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Biomedical subjects

Z Zheng

Publications and source records attributed to Z Zheng.

At least 127 records · Page 7Linked to original sources

In vivo investigation of blood compatibility of titanium oxide films.

Titanium oxide films were synthesized by ionbeam-enhanced deposition. The films were prepared by depositing titanium atoms and simultaneously bombarding them with Xe+ ions at an energy of 40 keV in an O2 environment. An in vivo investigation, which entailed implanting low-temperature isotropic pyrolytic carbon (LTI carbon) cylinders, widely used to fabricate artificial heart valves, and titanium-oxide-coated LTI carbon cylinders with diameters of 5 mm and thicknesses of 0.5 mm into the ventral aorta of dogs for 14 days, showed that the amount of thrombus on the titanium-oxide-coated LTI carbon was much less than that formed on the surface of LTI carbon alone. Scanning electron microscopy (SEM) was used to observe the morphology of thrombus. On the titanium oxide films no platelet aggregation was found, almost no red blood cells were damaged, and almost no fibrin was found on the surface. However, all three characteristics were found on the surface of LTI carbon alone, proving that the blood compatibility of titanium oxide films is better than that of LTI carbon and titanium-oxide-coated LTI carbon.

Animals↗

Allelic imbalance, including deletion of PTEN/MMACI, at the Cowden disease locus on 10q22-23, in hamartomas from patients with Cowden syndrome and germline PTEN mutation.

Cowden disease (CD) is a rare, autosomal dominant inherited cancer syndrome characterized by multiple benign and malignant lesions in a wide spectrum of tissues. While individuals with CD have an increased risk of breast and thyroid neoplasms, the primary features of CD are hamartomas. The gene for CD has been mapped by linkage analysis to a 6 cM region on the long arm of chromosome 10 at 10q22-23. Loss of heterozygosity (LOH) studies of sporadic follicular thyroid adenomas and carcinomas, both component tumors of CD, have suggested that the putative susceptibility gene for CD is a tumor suppressor gene. Somatic missense and nonsense mutations have recently been identified in breast, prostate, and brain tumor cell lines in a gene encoding a dual specificity phosphatase, PTEN/MMACI, mapped at 10q23.3. Furthermore, germline PTEN/MMACI mutations are associated with CD. In the present study, 20 hamartomas from 11 individuals belonging to ten unrelated families with CD have been examined for LOH of markers flanking and within PTEN/MMACI. Eight of these ten families have germline PTEN/MMACI mutations. LOH involving microsatellite markers within the CD interval, and including PTEN/MMACI, was identified in two fibroadenomas of the breast, a thyroid adenoma, and a pulmonary hamartoma belonging to 3 to 11 (27%) of these patients. The wild-type allele was lost in these hamartomas. Semi-quantitative PCR performed on RNA from hamartomas from three different tissues from a CD patient suggested substantial reduction of PTEN/MMACI RNA levels in all of these tissues. The LOH identified in samples from individuals with CD and the suggestion of allelic loss and reduced transcription in hamartomas from a CD patient provide evidence that PTEN/MMACI functions as a tumor suppressor in CD.

Chromosomes, Human, Pair 10↗

Jak-STAT pathway is involved in the induction of TNF-beta gene during stimulation by IL-2.

IL-2 is the major regulatory cytokine of the immune system. It plays a key role in T cell survival, growth and activation. IL-2 may induce the expression of multiple genes including some cytokine genes. The induction of these genes is triggered by different signal pathways, one of them being the Jak-STAT signal pathway. The genes regulated by this pathway remain to be determined. By studying IL-2-inducible genes, we have confirmed that the TNF-beta gene is one of the immediate early genes activated by IL-2. By analysis of the DNA sequences around 180-300 bases upstream of the transcription initiation point of the mouse TNF-beta gene, we demonstrate that there is a STAT5 binding site which is essential to the inducibility of the TNF-beta gene. Furthermore, in BA/F3 cells co-transfected with the STAT5A gene and IL-2R beta gene, the activation of the TNF-beta gene promoter by IL-2 was greatly promoted, whereas the TNF-beta gene promoter became IL-2-non-inducible if the STAT5A gene was substituted with a dominant negative STAT5A, i.e. a C-terminally truncated mutant. Taken together, our results show that the Jak-STAT signal pathway is involved in induction of the TNF-beta gene in cells stimulated by IL-2.

Animals↗

The role of polar interactions in the molecular recognition of CD40L with its receptor CD40.

CD40 Ligand (CD40L) is transiently expressed on the surface of T-cells and binds to CD40, which is expressed on the surface of B-cells. This binding event leads to the differentiation, proliferation, and isotype switching of the B-cells. The physiological importance of CD40L has been demonstrated by the fact that expression of defective CD40L protein causes an immunodeficiency state characterized by high IgM and low IgG serum levels, indicating faulty T-cell dependent B-cell activation. To understand the structural basis for CD40L/CD40 association, we have used a combination of molecular modeling, mutagenesis, and X-ray crystallography. The structure of the extracellular region of CD40L was determined by protein crystallography, while the CD40 receptor was built using homology modeling based upon a novel alignment of the TNF receptor superfamily, and using the X-ray structure of the TNF receptor as a template. The model shows that the interface of the complex is composed of charged residues, with CD40L presenting basic side chains (K143, R203, R207), and CD40 presenting acidic side chains (D84, E114, E117). These residues were studied experimentally through site-directed mutagenesis, and also theoretically using electrostatic calculations with the program Delphi. The mutagenesis data explored the role of the charged residues in both CD40L and CD40 by switching to Ala (K143A, R203A, R207A of CD40L, and E74A, D84A, E114A, E117A of CD40), charge reversal (K143E, R203E, R207E of CD40L, and D84R, E114R, E117R of CD40), mutation to a polar residue (K143N, R207N, R207Q of CD40L, and D84N, E117N of CD40), and for the basic side chains in CD40L, isosteric substitution to a hydrophobic side chain (R203M, R207M). All the charge-reversal mutants and the majority of the Met and Ala substitutions led to loss of binding, suggesting that charged interactions stabilize the complex. This was supported by the Delphi calculations which confirmed that the CD40/CD40L residue pairs E74-R203, D84-R207, and E117-R207 had a net stabilizing effect on the complex. However, the substitution of hydrophilic side chains at several of the positions was tolerated, which suggests that although charged interactions stabilize the complex, charge per se is not crucial at all positions. Finally, we compared the electrostatic surface of TNF/TNFR with CD40L/CD40 and have identified a set of polar interactions surrounded by a wall of hydrophobic residues that appear to be similar but inverted between the two complexes.

Amino Acid Sequence↗

Corynebacterium striatum chloramphenicol resistance transposon Tn5564: genetic organization and transposition in Corynebacterium glutamicum.

The clinical isolate Corynebacterium striatum M82B (formerly Corynebacterium xerosis M82B) carries the 50-kb R-plasmid pTP10 conferring resistance to the antibiotics chloramphenicol, erythromycin, kanamycin, and tetracycline. DNA sequence analysis of the chloramphenicol resistance region revealed the presence of the 4155-bp transposable element Tn5564. The ends of Tn5564 are identical 22-bp inverted repeats flanked by a 6-bp target site duplication. The central region of Tn5564 encodes the chloramphenicol resistance gene cmx, specifying a transmembrane chloramphenicol efflux protein, and an open reading frame homologous to transposases of insertion sequences identified in Arthrobacter nicotinovorans and Bordetella pertussis. Furthermore, the 1715-bp insertion sequence IS1513 encoding a putative transposase of the IS30 family is an integral part of Tn5564 and is located upstream of cmx. For transposon mutagenesis, Tn5564 was transferred to Corynebacterium glutamicum on a mobilizable Escherichia coli plasmid using RP4-mediated intergeneric conjugation. Transposition of Tn5564 in C. glutamicum occurred with a frequency of 3.3 x 10(-8) and resulted in an insertion into target sites containing the central palindromic tetranucleotide CTAG. A Tn5564-induced mutant strain of C. glutamicum was found to carry the transposon in the ftsZ gene region.

Amino Acid Sequence↗

Telomerase activation in nasopharyngeal carcinomas.

Nasopharyngeal carcinomas (NPC) are common in Hong Kong and southern China but rare in Western countries. Telomerase activation is common in human cancers but has not been reported previously in NPC. Telomerase activation in NPC was determined using the sensitive TRAP (telomerase rapid amplification protocol) assay in 45 nasopharyngeal biopsies (36 NPC, nine normal nasopharyngeal mucosae) in four xenografted NPC tumours established in nude mice and in five in vitro NPC cell lines. Telomerase activation is common in NPC and can be detected at high frequencies (85% in primary tumours and 100% in recurrent tumours). The frequency of telomerase activation was lowest in NPC biopsies without lymph node involvement (60%) compared with those with positive lymph node involvement (100%), and the difference is statistically significant (P < 0.05; Fisher exact test). All the xenografted NPC tumours and in vitro NPC cell lines were strongly positive for telomerase activity. Our results suggest that telomerase activation is common in NPC and it may be useful as a diagnostic marker in the detection of tumour cells in nasopharyngeal biopsies. The high frequency of telomerase activation in stage I NPC (80% positive) suggests that it is an early event in tumour progression.

Adolescent↗

Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation.

The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403 amino acid dual specificity phosphatase (protein tyrosine phosphatase; PTPase), was shown recently to play a broad role in human malignancy. Somatic PTEN deletions and mutations were observed in sporadic breast, brain, prostate and kidney cancer cell lines and in several primary tumours such as endometrial carcinomas, malignant melanoma and thyroid tumours. In addition, PTEN was identified as the susceptibility gene for two hamartoma syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD families and seven BZS families was screened for germline PTEN mutations. PTEN mutations were identified in 30 of 37 (81%) CD families, including missense and nonsense point mutations, deletions, insertions, a deletion/insertion and splice site mutations. These mutations were scattered over the entire length of PTEN , with the exception of the first, fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD mutations identified in this exon. Seven of 30 (23%) were within the core motif, the majority (five of seven) of which were missense mutations, possibly pointing to the functional significance of this region. Germline PTEN mutations were identified in four of seven (57%) BZS families studied. Interestingly, none of these mutations was observed in the PTPase core motif. It is also worthy of note that a single nonsense point mutation, R233X, was observed in the germline DNA from two unrelated CD families and one BZS family. Genotype-phenotype studies were not performed on this small group of BZS families. However, genotype-phenotype analysis inthe group of CD families revealed two possible associations worthy of follow-up in independent analyses. The first was an association noted in the group of CD families with breast disease. A correlation was observed between the presence/absence of a PTEN mutation and the type of breast involvement (unaffected versus benign versus malignant). Specifically and more directly, an association was also observed between the presence of a PTEN mutation and malignant breast disease. Secondly, there appeared to be an interdependent association between mutations upstream and within the PTPase core motif, the core motif containing the majority of missense mutations, and the involvement of all major organ systems (central nervous system, thyroid, breast, skin and gastrointestinal tract). However, these observations would need to be confirmed by studying a larger number of CD families.

Chromosome Mapping↗

Human cytomegalovirus glycoprotein B contains autonomous determinants for vectorial targeting to apical membranes of polarized epithelial cells.

We previously reported that human cytomegalovirus (CMV) glycoprotein B (gB) is vectorially transported to apical membranes of CMV-infected polarized human retinal pigment epithelial cells propagated on permeable filter supports and that virions egress predominantly from the apical membrane domain. In the present study, we investigated whether gB itself contains autonomous information for apical transport by expressing the molecule in stably transfected Madine-Darby canine kidney (MDCK) cells grown on permeable filter supports. Laser scanning confocal immunofluorescence microscopy and domain-selective biotinylation of surface membrane domains showed that CMV gB was transported to apical membranes independently of other envelope glycoproteins and that it colocalized with proteins in transport vesicles of the biosynthetic and endocytic pathways. Determinants for trafficking to apical membranes were located by evaluating the targeting of gB derivatives with deletions in the lumen, transmembrane (TM) anchor, and carboxyl terminus. Derivative gB(Delta717-747), with an internal deletion in the luminal juxtamembrane sequence that preserved the N- and O-glycosylation sites, retained vectorial transport to apical membranes. In contrast, derivatives that lacked the TM anchor and cytosolic domain (gBDelta646-906) or the TM anchor alone (gBDelta751-771) underwent considerable basolateral targeting. Likewise, derivatives lacking the entire cytosolic domain (gBDelta772-906) or the last 73 amino acids (gBDelta834-906) showed disrupted apical transport. Site-specific mutations that deleted or altered the cluster of acidic residues with a casein kinase II phosphorylation site at the extreme carboxyl terminus, which can serve as an internalization signal, caused partial missorting of gB to basolateral membranes. Our studies indicate that CMV gB contains autonomous information for apical targeting in luminal, TM anchor, and cytosolic domain sequences, forming distinct structural elements that cooperate in vectorial transport in polarized epithelial cells.

Amino Acid Sequence↗

Cell interaction molecules utilized in bone marrow.

Many aspects of blood cell formation can now be modeled in culture and rapid progress is being made in understanding how blood cell precursors interact with unique components of their environment. This brief review considers some cell interaction molecules that may be important for controlling the position of cells within, as well as their egress from, bone marrow.

B-Lymphocytes↗

Studies on chemical constituents and immunological function activity of hairy root of Astragalus membranaceus.

Using a large-scale culture technique, the hairy roots of Astragalus membranaceus were produced with a yield reaching 10 g/L. The results from RP-HPLC detection showed that the contents of crude saponin and astragaloside i.v. in the hairy roots were 5.81% and 0.14%, respectively. Six isoflavonoid compounds were also determined. Polysaccharide analysis showed that the total polysaccharide content in the hairy roots was 22.97%; of this content, acidic 8.29% and soluble 14.88%. In comparison with the dry roots, the hairy roots contained higher crude saponin and soluble polysaccharide contents, similar astragaloside i.v. content and lower contents of 6 isoflavonoids, total and acidic polysaccharides, showing that the quality of both types of roots was similar. Regaining the immunity function of rats with low immunity after feeding the aqueous extract of the hairy roots produced by large-scale culture showed that its capacity was similar to the dry roots of A. membranaceus in increasing the immunity function. The results in this paper give evidence that the hairy roots may be a new source of A. membranaceus.

Animals↗

[Heart function and clinical observations of patients with severe congestive heart failure treated with milrinone].

To evaluate the clinical effects of milrinone in patients with severe heart failure, heart function and clinical observations were performed on 25 patients with severe congestive heart failure treated with domestic intravenous milrinone for 15 days. Results showed that the total response rate to milrinone was 96% while 60% of them had significant improvement. Heart function and diameter of left atrial, left ventricle, and right ventricle were measured by pulsed Doppler and M-mode echocardiographg before and after the treatment. The systolic function of the left ventricle (such as SV, CO, EF, FS, IVST, PLVWT) was significantly improved. The diastolic function of the left ventricle (such as E peak, A peak, IRT) was also improved. Diameter of left atrial, left ventricle, and right ventricle was significantly reduced. The heart rate and blood pressure remained unchanged. No obvious side-effect was found in our observation. The domestic intravenous milrinone is a drug of choice for the management of patients with severe congestive heart failure.

Adult↗

[Effects of fat emulsion on serum lipid, apo A I, apo B100, LCAT, KBR of postoperative patients with liver disorder].

Twenty post-operative patients with liver disorder were divided randomly into two groups. Ten of them received mean 0.82 g.kg-1.d-1 fat emulsion(42% of the total calorie), and the other ten received mean 1.72 g.kg-1.d-1 fat emulsion (52% of the total calorie) via vein during 5 post-operative days. Their serum lipid, apoA I, apoB100, ketone body ratio (KBR), fat clearance, LCAT and so on were investigted. The results suggest that it is safe for liver-disordered patients with slight or even moderate abnormality of liver function to receive mean 0.82 g.kg-1.d-1 and 1.72 g.kg-1.d-1 fat emulsion after operation and the use of mean 1.72 g.kg-1.d-1 fat emulsion will do no harm but good to liver function.

Adult↗

[Molecular cloning and sequencing of genes encoding MSP2 isolates strains from two of Plasmodium falciparum from Chinese patients with cerebral malaria].

OBJECTIVE: To provide the scientific evidence for designing safe and effective vaccines of human cerebral malaria. METHODS: Genomic DNA samples of two isolated Plasmodium falciparum isolate strains prepared directly from 5 cases of cerebral malaria patients' blood in mengla County, Yunnan Province (CMH/YN) and in Yingjiang County, Yunnan Province (CYJ/YN) were used for polymerase chain reaction (PCR) amplification and the two pairs of oligonucleotides for the highly conserved genes encoding FC27 merozoite surface protein 2 (MSP2) of Papua New Guinea strain of Plasmodium falciparum were used as primers. The PCR products were digested with BamH1 and Hind III respectively, and the generated fragment MSP2 were cloned into M13mp18 and M13mp19 vectors and their DNA was analyzed as the templates for DNA sequencing by the dideoxy chain-termination method. RESULTS: Compared with the published findings, FC27, K1, IC1 and CAMP sequences, DNA sequences of MSP2 from two isolated CMH/YN and CYJ/YN of Plasmodium falciparum strains from Chinese patients with cerebral malaria contained identical genes composed of 800 bp, encoding 264 amino acid, which were highly homologous up to 98.8% with that of FC27, K1 strain other than the IC1, CAMP strain. CONCLUSION: It is the first record of DNA sequencing of MSP2 determined from two isolated CMH/YN and CYJ/YN of Plasmodium falciparum strains from Chinese patients with cerebral malaria, MSP2 mutation may be one factor leading to the localized cerebral damage which causes clinical coma of human cerebral malaria.

Amino Acid Sequence↗

[Blood supply reestablishment of avascular necrosis of femoral head with digital subtraction angiography].

OBJECTIVE: To use digital subtraction angiography (DSA) to evaluate blood supply reestablishment after the treatment of the avascular necrosis of femoral head (ANFH) by using the vascularized iliac periosteum with deep iliac circumflex artery (DICA) and vein pedicle. METHODS: Seldinger method was used to puncture femoral artery interpate of 20 patients with pre and postoperative ANFH. 6.5 F Cobrn conduct was optionally used and put directly into DICA and then contrast medium, was injected for observation of blood vessel. RESULTS: Before operation, the position of DICA was found constant, 3 to 7 branches termity among the crest part of iliac bone. Three weekes after operation, DICA was found wider than that before operation, but the blood flow speed remained almost the same and its termity was distributed evenly inside the femoral head and looked like a bird's net. Three months after operation, the blood vessel was still wider, but blood flowed faster and its termity changed roundish, and the bird's net changed greatly and capillaries reached the subchoronal zone of femoral head. CONCLUSION: Blood flow was well reestablished after the treatment of ANFH by DSA. It can be easily checked with less damage, large liability, and clear picture.

Adult↗

[Comparison of polymerase chain reaction and culture method for assaying ureaplysma urealyticum in urogenital specimens].

OBJECTIVE: A comparison study of polymerase chain reaction (PCR) and culture method were used to detect urogenital ureaplasma urealyticum. METHODS: Urogenital specimens from 116 patients were assayed in parallel by the two methods. RESULTS: 46 cases were positive by PCR, 42 cases positive by culture, and UuDNA were dedected in 42 cases of the 45 positive by culture. Compared with culture, the sensitivity and specificity of PCR were 93.3% and 94.4%, respectively. The positive rate of both methods were comparable (P > 0.05). CONCLUSIONS: The PCR technique to detect Uu is highly sensitive and specific. As for culture method, it takes the advantage of being relative simple and takes much less time to give results.

Adolescent↗

[Determination of 6 isoflavonoids in the hairy root cultures of Astragalus membranaceus by HPLC].

An accurate RP-HPLC method for the determination of 10-hydroxy-3, 9-dimethoxypeterocarpan, (3R) 8,2'-dihydroxy-7,4'-dimethoxyisoflavan, formonenetin (7-hydroxy-4'-methoxyisoflavone), 8, 3'-dihydroxy-7, 4'-dimethoxy-isoflavone, 2'-hydroxy-3', 4'-dimethoxyisoflavan-7-O-glucopyranoside and alycosin (7,3'-dihydroxy-4'-methoxyisoflavone) in the hairy root cultures of Astragalus membranaceus was developed. Among them, 10-hydroxy-3, 9-dimethoxypeterocarpan, (3R) 8,2'-dihydroxy-7,4'-dimethoxyisoflavan and 8,3'-dihydroxy-7,4'-dimethoxyisoflavone were new compounds in Astragalus membranaceus. The analytical column was Nucleosil C18. The mobile phases were methanol-water = 3:2 and 1:1 (v/v). The detection wavelengths were 254 nm and 280 nm. Calibration graphs were rectilinear between 2.5 micrograms and 12.5 micrograms. The recoveries were between 96.47% and 103.33%. The relative standard deviations (RSDs) of measurement precision test were 2.57%-6.52%. The flavonoid contents in the hairy root cultures were between 0.0005% and 0.0065% (dry weight).

Astragalus propinquus↗

[Determination of naftopidil and its main metabolite in plasma by high-performance liquid chromatography].

A method was developed for the determination of naftopidil (NAF) and its main metabolite desmethyl-naftopidil (DMN) in plasma by HPLC. A mixture of methanol, acetonitrile and 0.02 mol.L-1 K2HPO4 solution was used as mobile phase. Stationary phase was RP-C18. Propranolol was chosen as internal standard (IS), and the detector wavelength was 240 nm. Under these conditions, the retention times of IS, DMN and NAF were 6.2, 7.6 and 10.5 min respectively. Absolute recoveries from plasma were up to 93.4% (IS), 76.8% (DMN) and 80.2% (NAF). The assay was linear for DMN and NAF in the range of 10-800 ng.ml-1 plasma concentration, gamma = 0.9998. The lowest detection limits were 8 ng.ml-1 (DMN) and 5 ng.ml-1 (NAF), and the precisions within-day and day-to-day were no more than 6.3% for MDN and 11.6% for NAF. The drug concentration-time pattern of these two substances was also studied with this method. Result showed that naftopidil was quickly absorbed after p.o. and the concentration-time data were fitted to two compartment model, with half life (T1/2 beta) of 8.13 h.

Adrenergic alpha-Antagonists↗