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Biomedical subjects

Z Zhang

Publications and source records attributed to Z Zhang.

At least 145 records · Page 8Linked to original sources

Helicobacter pylori cagA and vacA cytotoxin genes in Changsha, China.

Cytotoxin-associated protein (cagA) and the vacuolating cytotoxin (vacA) encoded by cagA and vacA genes are virulence determinants of Helicobacter pylori. In earlier studies among Chinese patients, all H. pylori strains were cagA-positive and vacAs1a/m2 type. Here, we determine the cagA, vacA and allele status of H. pylori strains isolated from patients with upper gastrointestinal symptoms in Changsha, China. Forty strains of H. pylori isolated from patients with peptic ulcer disease between March 1997 and August 1999 were recovered from storage at -80 degrees C and studied by the polymerase chain reaction (PCR) for cagA and vacA genotypes. cagA was positive in 75% of H. pylori isolates. Patients with peptic ulcer demonstrated cagA in 83% (15/18), compared with 68% (15/22) patients with superficial gastritis. vacAs1 allele was carried in 82.5% (33/40) isolates, of which 52.5% (21/40) were subtype vacAs1a/m2 and 17.5% (7/40) were subtype vacAs1b/m2.

Antigens, Bacterial↗

Computational analysis of micron-particle deposition in a human triple bifurcation airway model.

Steady laminar axisymmetric inhalation flow and wall deposition of micron-size particles in representative triple bifurcation airways have been simulated using a commercial finite-volume code with user-enhanced programs. Assuming spherical non-interacting particles (3 microm</=d(p)</=7 microm), various inlet Reynolds numbers (Re=500-2000) and Stokes numbers (St=0.02-0.23) were considered. The resulting particle deposition patterns were analyzed and then summarized in terms of deposition efficiencies, i.e. DE=DE(Re,St) Surprisingly high DE-values occur at relatively low Reynolds numbers (e.g., Re=500) in the third bifurcation. The quantitative results are of interest to researchers either conducting health risk assessment studies for inhaled particulate pollutants or analyzing drug aerosol inhalation and deposition at desired lung target sites.

Administration, Inhalation↗

Screening of upper digestive tract cancer with dilute hydrochloric acid and alcohol in a Chinese high-risk population--a follow-up study of 12 years.

This is a 12-year follow-up study on screening with a mixture of 2% hydrochloric acid and 18% alcohol for upper digestive tract cancer in a Chinese high-risk population. A public screening for upper digestive tract cancer was conducted from November 1979 to May 1984 by giving a mixture of 2% hydrochloric acid and 18% alcohol to 7280 subjects in high-risk population in Yaocun village, Linxian County, Henan province. The subjects were given 15 ml of this mixture in the morning or at noon before lunch when fasting. Five minutes later, irritative reactions (retrosternal discomfort, warmth, pain or pyrosis) was felt in subjects suffering from oesophageal cancer, oesophagitis, gastritis, mucosal dysplasia or ulcer (positive group). Those with normal oesophageal or gastric mucosa felt nothing (negative group). The overall positive rate was 23.2% (1689/7280). In oesophageal or gastric cancer subjects, the positive rate of these symptoms was 88.7%. In subjects with mucosal dysplasia, it was 71.2%. A total of 26 upper digestive tract cancer patients were found. As a result of 12 years' follow-up, 271 persons with upper digestive tract cancer among the 1689 positive group subjects have been discovered, giving an annual morbidity rate of 1.34%. Among the 5591 negative group subjects, 136 persons have been found to suffer from this cancer, giving an annual morbidity rate of 0.2%. This illustrated that the annual morbidity rate of upper digestive tract cancer in the positive group was 6.65 times of that of the negative group ( <0.0001). In conclusion, screening of upper digestive tract cancer with dilute hydrochloric acid in alcohol is simple, safe, non-traumatic, effective and readily acceptable in a high-risk area in China. It may be feasible in other parts of the world, especially the developing countries.

Central Nervous System Depressants↗

Quantities of infectious virus and viral RNA recovered from sheep and cattle experimentally infected with foot-and-mouth disease virus O UK 2001.

The profiles of virus production and excretion have been established for sheep experimentally infected with the UK 2001 strain of foot-and-mouth disease (FMD) virus by inoculation and by direct and intensive contact. Virus replicated rapidly in the inoculated sheep, from which a peak infectivity of airborne virus of 10(4.3) TCID(50) per sheep per 24 h was recovered. Around 24 h later, contact-infected sheep excreted airborne virus maximally. Similar amounts of airborne virus were recovered from cattle. The excretion of virus by the sheep under these conditions fell into three phases. First, a highly infectious period of around 7-8 days. Second, a period of 1-3 days soon afterwards when trace amounts of viral RNA were recovered in nasal and rectal swabs. Third, at 4 weeks after exposure, the demonstration, by tests on oesophageal-pharyngeal samples, that 50% of the sheep were carriers. The implications of the results and the variable role that sheep may play in the epidemiology of FMD are discussed.

Aerosols↗

Selective plasma filtration for treatment of fulminant hepatic failure induced by D-galactosamine in a pig model.

BACKGROUND: Plasma exchange may be useful for treating patients with fulminant hepatic failure but during the procedure growth factors that are important for hepatic regeneration are discarded. Addition of a selective plasma filter to the plasmapheresis circuit could eliminate protein bound toxic substances and retain growth factors for hepatic regeneration. This process is called selective plasma filtration. AIMS: To determine if selective plasma filtration could be a useful treatment modality for fulminant hepatic failure. METHODS: The system was tested in five groups of pigs with fulminant hepatic failure induced by galactosamine: group I, diseased control group (n=5); group II, sham control, (n=6); group III, plasma exchange (n=6); group IV, treatment with AC-1770 selective plasma filter (n=7); and group V, treatment with AC-1730 selective plasma filter which had a smaller pore size than AC-1770 (n=7). Fresh pig plasma was given to replace filtered plasma in pigs of groups III, IV, and V. Treatment was initiated 48 hours after administration of 0.75 g/kg galactosamine. The efficacy of selective plasma filtration was assessed by survival rate and improvement in haematological, biochemical, and immunohistological parameters. RESULTS: Pigs treated with AC-1770 or AC-1730 selective plasma filters survived longer than the other groups (group I: 55 (10) hours; group II: 68 (7) hours; group III: 91 (10) hours; group IV: 269 (156) hours; group V: 950 (555) hours). One pig in group IV survived for 50 days; one pig in group V survived for 77 days and another pig in group V is still alive (>150 days). After treatment, plasma levels of aspartate aminotransferase, bilirubin, bile acid, ammonia, lactate dehydrogenase, and alpha-glutathione-S-transferase decreased. Substantial amounts of tumour necrosis factor alpha (TNF-alpha) and endotoxin were found in the filtrate. The selective plasma filtration groups retained significantly higher amounts of hepatocyte growth factor than plasma exchange alone. Similar TNF-alpha clearance was observed in the selective plasma filtration groups and the plasma exchange group. On day 4, significant improvement in liver function, as measured by the indocyanine green clearance test, was observed in groups IV and V but not in the other groups. A higher regeneration index of hepatocytes was also observed in the groups treated with AC-1770 and AC-1730 selective plasma filters. CONCLUSION: Selective plasma filtration improved survival time and expedited liver regeneration in pigs with fulminant hepatic failure.

Animals↗

APOE genotypes and disease severity in multiple sclerosis.

Apolipoprotein E (opoE) is involved in the transport of lipids necessary for membrane repair and is encoded by a gene on chromosome 19q13, a region positive for linkage in two multiple sclerosis (MS) genome-wide screens. The APOE epsilon4 allele confers susceptibility to both familial and sporadic Alzheimer's disease (AD). Carriage of epsilon4 is associated with defective dendritic remodeling in AD, and with unfavorable clinical outcome in head trauma and cerebrovascular disease. According to the results of previous studies, APOE epsilon4 does not increase the risk of developing MS, but it may influence disease progression and ultimate disability. From a total cohort of over 900 MS patients, we compared APOE epsilon2-4 genotypes in, roughly, the cohort's least disabled and most disabled septiles. 'Benign MS' (n=124) was defined as an Expanded Disability Status Scale (EDSS) score of 3.0 or less, despite at least 10 years of disease duration, and 'severe MS' (n=140) as the attainment of an EDSS score of 6.0 within 8 years of disease onset. We found no significant differences in genotype or phenotype frequencies between the benign-MS and severe-MS septiles; however, the risk conferred by epsilon4 rose progressively upon comparison of carriage rates in more narrowly defined anti-podal quantiles.

Adolescent↗

Chimerism analysis in sex-mismatched murine transplantation using quantitative real-time PCR.

Marine experimental stem cell transplantations require the accurate discrimination and quantification of donor cells from host cells. A Y-chromosome-specific, quantitative real-time PCR (kinetic PCR) protocol for blood-derived DNA was developed. The assay sensitivity was extremely high with accurate detection of only 10 pg (six copies of Y target DNA) in a variable background of female DNA background ranging from 2.5 to 50 ng. The dynamic range of the assay provided accurate results ranging from 2.2 x 10(-2)% to 100% of male DNA in female background. The kinetic PCR assay can be used in all mouse strains, and a sample size as low as 2.5 ng total DNA is sufficient for analysis. Therefore, kinetic PCR allows engraftment kinetic studies on repeated blood draws of individual animals with no need for sacrifice. Compared to conventional PCR, the assay is much simplified, as neither the accurate adjustment of sample DNA concentration nor a post-reaction analysis procedure is required. The procedure is simple, free of radioactivity, and permits a throughput of 500-600 reactions per day.

Animals↗

Electrochemistry and spectroscopy study on the interaction of microperoxidase-11 with lipid membrane.

The interaction of microperoxidase-11 (MP11) with cationic lipid vesicles of didodecyldimethylammonium bromide (DDAB) induces an alpha-helical conformation from random coil conformations in solution and this change then makes heme macrocycle more distorted. DDAB-induced MP11 conformations were investigated by cyclic votammetry (CV), circular dichroism (CD) and UV-vis spectrometry. All results indicate that the binding of MP11 in solution to DDAB vesicles and the ordered structure formation are driven by mostly electrostatic interaction between negatively charged residues in the undecapeptide and positively charged lipid headgroups on the membrane surface. Upon binding to DDAB, its half-peak potential was also changed. The mechanism of the interaction between MP11 and DDAB was also discussed.

Circular Dichroism↗

[Study on the stroma of patients with paroxysmal nocturnal hematoglobinuria].

OBJECTIVE: To investigate the relationship between the stroma of bome marrow and the abnormality of hematopoiesis in patients with paroxysmal nocturnal hematoglobinuria (PNH). METHODS: The bone marrow stromata from PNH patients was compared with those from normal volunteers in aspects of their CFU-F formation and hematopoietic sustentation for normal CD34+ cells. The stromal IL-6 and TNF-alpha mRNA expression in patients and normal volunteers was also measured by RT-PCR(self beta-actin as contrast). RESULTS: (1) The CFU-F formation ability in PNH patients was very similar to that in normal volunteers (P > 0.05). (2) The bone marrow stromata from patients with PNH had the same hematopoietic maintenance compared to those from normal controls (P > 0.05). (3) The stomal IL-6 and TNF-alpha mRNA expression was similar in PNH patients and in normal volunteers (P > 0.05). CONCLUSION: The CFU-F formation capacity of bone marrow fibroblast was normal in PNH patients. The stromata in patients with PNH had normal hematopoietic maintainence to the normal CD34+ cells. The mRNA expression of IL-6 and TNF-alpha in PNH stromata was almost normal.

Adolescent↗

In vitro evidence for an intracellular site of angiotensin action.

To differentiate the relative effects of nuclear and cell surface angiotensin II (Ang II) receptors, we mutated the angiotensinogen cDNA by removing the signal sequence-encoding region to produce a nonsecreted form of angiotensinogen [Ang(-S)Exp]. Rat hepatoma cells (which produce renin and angiotensin-converting enzyme mRNAs) were stably transfected with Ang(-S)Exp/pSVL (or a corresponding control) expression plasmid, and mitotic indices were measured for stably transfected cell lines. Experimental clonal cell lines demonstrate an average of 33+/-4.4% (P<0.001) increase in percentage-labeled nuclei compared with control cell lines. The mitogenic effect is blocked by 10(-6) mol/L losartan and by 1 micromol/L renin antisense phosphorothioate oligomers but not by 10(-6) mol/L candesartan. In addition, phenylarsine oxide, which blocks angiotensin receptor internalization, abolishes the losartan inhibitory effect, suggesting that after cell-surface receptor-mediated endocytosis, losartan blocks Ang II nuclear receptors. PDGF mRNA levels are elevated 2.2-fold in Ang(-S)Exp transfected cell lines; addition of anti-PDGF antibodies to the culture medium partially blocks the mitogenic effect of Ang(-S)Exp, while anti-Ang II antibodies have no effect. These results suggest that the Ang(-S)Exp growth effect is due, in part, to autocrine/paracrine stimulation by secreted PDGF after Ang II/Ang II receptor intracellular interactions. We further demonstrate that these cells produce the alternative renin transcript, renin 1A, which apparently lacks a signal sequence and is maintained intracellularly. Collectively, these studies of cultured cells suggest that some cell types may possess components of the renin-angiotensin system that permit intracellular processing of angiotensinogen to Ang II and that Ang II generated intracellularly may be mitogenic.

Alternative Splicing↗

Nitric oxide modulates cardiac Na(+) channel via protein kinase A and protein kinase G.

We directly tested the effects of nitric oxide (NO) on Na(+) channels in guinea pig and mouse ventricular myocytes using patch-clamp recordings. We have previously shown that NO donors have no observed effects on expressed Na(+) channels. In contrast, NO (half-blocking concentration of 523 nmol/L) significantly reduces peak whole-cell Na(+) current (I(Na)) in isolated ventricular myocytes. The inhibitory effect of NO on I(Na) was not associated with changes in activation, inactivation, or reactivation kinetics. At the single-channel level, the reduction in macroscopic current was mediated by a decrease in open probability and/or a decrease in the number of functional channels with no change in single-channel conductance. Application of cell permeable analogs of cGMP or cAMP mimics the inhibitory effects of NO. Furthermore, the effects of NO on I(Na) can only be blocked by inhibition of both cGMP and cAMP pathways. Sulfhydryl-reducing agent does not reverse the effect of NO. In summary, although NO exerts its action via the known guanylyl cyclase (GC)/cGMP pathway, our findings provide evidence that NO can mediate its function via a GC/cGMP-independent mechanism involving the activation of adynylyl cyclase (AC) and cAMP-dependent protein kinase.

3',5'-Cyclic-AMP Phosphodiesterases↗

Effect of long-term estrogen deprivation on apoptotic responses of breast cancer cells to 17beta-estradiol.

BACKGROUND: High doses of estrogen can promote tumor regression in postmenopausal women with hormone-dependent breast cancer, but the mechanism is unknown. We investigated the molecular basis of this process by using LTED cells, which were derived by growing MCF-7 breast cancer cells under long-term (6-24 months) estrogen-deprived conditions. METHODS: We treated LTED and MCF-7 cells with various concentrations of 17beta-estradiol (estradiol) and assayed their growth by counting the cells and measured apoptosis by annexin V staining and DNA fragmentation. Using western blot analysis, we also examined the expression of the apoptosis-inducing system of the Fas death receptor protein and its ligand, FasL, in these cells. To assess the involvement of Fas and FasL in the induction of apoptosis in LTED cells, we used activating anti-Fas antibodies and the universal caspase inhibitor Z-VAD. Finally, we examined the expression of Fas protein in E8CASS and BSK3 cells, two other cell lines derived by depriving MCF-7 cells of estrogen long term, and the responses of these cells to high-dose estradiol. All statistical tests were two-sided. RESULTS: High concentrations of estradiol (>or=0.1 nM) resulted in a statistically significant, 60% reduction in the growth of LTED cells (P< .001) and in a sevenfold increase in apoptosis (P< .001) as compared with levels in vehicle-treated cells. Both LTED and MCF-7 cells expressed FasL, but only LTED cells expressed Fas. Treatment of LTED cells with 0.1 nM estradiol increased the expression of FasL. Activating anti-Fas antibodies increased apoptosis of LTED cells, which was further stimulated by estradiol. Z-VAD blocked estradiol-induced apoptosis. E8CASS cells, which express Fas protein, but not BSK3 cells, which do not, also responded to 0.1 nM estradiol by increasing apoptosis. CONCLUSION: Tumor regression induced by high-dose estrogen therapy in postmenopausal woman may result from estrogen activation of Fas-mediated apoptosis.

Apoptosis↗

Hydrogen peroxide mediates activation of nuclear factor of activated T cells (NFAT) by nickel subsulfide.

Nickel compounds induce cell transformation in cell culture models and tumor formation in experimental animals. However, the molecular mechanisms by which nickel compounds induce tumors are not yet well understood. The present study found that exposure of cells to either Ni(3)S(2) or NiCl(2) could result in specific transactivation of nuclear factor of activated T cells (NFAT), although it did not show any activation of p53 or AP-1. Furthermore, nickel compounds were also able to cause generation of reactive oxygen species (ROS). The scavenging of nickel-induced H(2)O(2) with N-acety-L-cyteine (a general antioxidant) or catalase, or the chelation of nickel with deferoxamine, resulted in inhibition of NFAT activation. In contrast, pretreatment of cells with sodium formate (an .OH radical scavenger) or superoxide dismutase (an O(-.)(2) radical scavenger) did not show any inhibitory effects. These results demonstrate that nickel compounds are able to induce NFAT activation, and that the mechanism of NFAT activation seems to be mediated by the generation of H(2)O(2) by these metal compounds. This study should help us understand the signal transduction pathways involved in carcinogenic effects of these nickel compounds.

Acetylcysteine↗

[Relationship between indigenous microflora of posterior pharyngeal wall and pharyngitis].

OBJECTIVE: To investigate the relationship between the abundance and density of the normal flora in the mucous membrane of posterior pharyngeal wall and pharyngitis. METHODS: A total of 410 samples of posterior pharyngeal wall were received from patients with acute and chronic pharyngitis and normal persons living in Hohhot Area, Inner Mongolia, from September 2000 to April 2001. Locational, qualitative, and quantitative analyses of the micro-flora were made. RESULTS: There were 6-9 species of bacteria, belonging to 4-5 genuses, in normal persons' pharyngeal wall. alpha-hemolytic streptococcus, Neisseria, Corynebacterium, Staphylococcus, Streptococcus anaerobius, and fusiform bacillus accounted for 40%-60%, 20%-30%, 5%-10%, 4%-8%, and 0%-40% respectively of the cultured microorganisms. Hemophilus influenzae accounted for 65% of the pathogenic bacteria in acute pharyngitis. There is a close relationship between the succession of the invading organisms and indigenous micro-flora and the occurrence and development of acute pharyngitis. CONCLUSION: The internal disorder of the proper microflora in the mucous membrane of posterior pharyngeal wall is a characteristic indicator of chronic inflammation of pharynx.

Bacteria↗

senseless repression of rough is required for R8 photoreceptor differentiation in the developing Drosophila eye.

An outstanding model to study how neurons differentiate from among a field of equipotent undifferentiated cells is the process of R8 photoreceptor differentiation during Drosophila eye development. We show that in senseless mutant tissue, R8 differentiation fails and the presumptive R8 cell adopts the R2/R5 fate. We identify senseless repression of rough in R8 as an essential mechanism of R8 cell fate determination and demonstrate that misexpression of senseless in non-R8 photoreceptors results in repression of rough and induction of the R8 fate. Surprisingly, there is no loss of ommatidial clusters in senseless mutant tissue and all outer photoreceptor subtypes can be recruited, suggesting that other photoreceptors can substitute for R8 to initiate recruitment and that R8-specific signaling is not required for outer photoreceptor subtype assignment. A genetic model of R8 differentiation is presented.

Animals↗

Activation of melatonin receptor increases a delayed rectifier K+ current in rat cerebellar granule cells.

The present study was initiated to investigate the effect of melatonin on K+ current in rat cerebellar granule cells for 2 to 6 days in culture (DIC). The whole-cell configuration of the conventional patch-clamp technique was used to record the outward K+ current. Two types of outward K+ current, a transient outward K+ current and a delayed rectifier K+ current, were separated by different voltage protocols and a specific blocker of K+ channel. Application of melatonin (10 microM) by a brief pressure ejection induced a significant and reversible increase of the delayed rectifier K+ current amplitude in 78% of the cells tested. The activated effect of melatonin on the K+ current was independent of the time in culture, and the percentage of activation remained at a relatively stable level from 2 DIC to 6 DIC; but that was dependent on the concentration of melatonin applied. The activation of the K+ current induced by melatonin presented no desensitization after repeated application of melatonin. The effect of melatonin on the K+ current can be mimicked by 2-iodomelatonin, a melatonin receptor agonist. With the addition of guanosine-5'-O-(3-thiophosphate) in the pipette solution, melatonin caused a stronger activation effect on the K+ channels, and an irreversible increase of the current amplitude in some granule cells tested. Pretreatment of cells with PTX suppressed the action of melatonin on the K+ current in most granule cells studied. In addition, the activation curves and inactivation curves tested with the steady-state activation and inactivation protocols were unchanged by melatonin, suggesting that melatonin did not modulate the channel's activation and inactivation properties. Our results demonstrated the presence of a functional melatonin receptor in cultured cerebellar granule cells from neonatal cerebellum. Activating the receptor can modulate the outward K+ currents by coupling to a PTX-sensitive G protein.

Animals↗