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Biomedical subjects

Z Gu

Publications and source records attributed to Z Gu.

At least 109 records · Page 6Linked to original sources

3'-Azido-3'-deoxythymidine (AZT) mediates cross-resistance to nucleoside analogs in the case of AZT-resistant human immunodeficiency virus type 1 variants.

Difficulties in deciphering the mechanisms of 3'-azido-3'-deoxythymidine (AZT)-resistance by human immunodeficiency virus type 1 (HIV-1) variants are due in part to an inability to reconstitute resistance in vitro using AZT-resistant reverse transcriptases. We decided to characterize mechanisms of AZT resistance in tissue culture infections by studying the ability of drug-resistant viruses to synthesize viral DNA in the presence or absence of drug. Through use of PCR amplifications, we discovered an AZT-mediated stimulation of reverse transcription by AZT-resistant viruses carrying the M41L and T215Y mutations that can apparently override the inhibitory effects of AZT-5'-triphosphate. In addition, the presence of AZT also causes viruses containing the M41L and T215Y substitutions to have diminished sensitivity to other nucleoside analogs (i.e., ddC, ddI, and d4T). This AZT-mediated cross-resistance may help to explain the virological failure of treatment regimens that included ddI plus AZT or ddC plus AZT in situations in which the T215Y and/or M41L mutations were present (F. Brun-Vézinet, C. Boucher, C. Loveday, D. Descamps, V. Fauveau, J. Izopet, D. Jeffries, S. Kaye, C. Krzyanowski, A. Nunn, R. Schuurman, J. M. Seigneurin, C. Tamalet, R. Tedder, J. Weber, and G. J. Weverling, Lancet 350:983-990, 1997). Our results suggest that the use of AZT may be contraindicated in those patients for whom resistance to this compound (M41L and/or T215Y) has been demonstrated.

Anti-HIV Agents↗

Activation of c-myc gene expression by tumor-derived p53 mutants requires a discrete C-terminal domain.

Mutation of the p53 tumor suppressor gene is the most common genetic alteration in human cancer, and tumors that express mutant p53 may be more aggressive and have a worse prognosis than p53-null cancers. Mutant p53 enhances tumorigenicity in the absence of a transdominant negative mechanism, and this tumor-promoting activity correlates with its ability to transactivate reporter genes in transient transfection assays. However, the mechanism by which mutant p53 functions in transactivation and its endogenous cellular targets that promote tumorigenicity are unknown. Here we report that (i) mutant p53 can regulate the expression of the endogenous c-myc gene and is a potent activator of the c-myc promoter; (ii) the region of mutant p53 responsiveness in the c-myc gene has been mapped to the 3' end of exon 1; (iii) the mutant p53 response region is position and orientation dependent and therefore does not function as an enhancer; and (iv) transactivation by mutant p53 requires the C terminus, which is not essential for wild-type p53 transactivation. These data suggest that it may be possible to selectively inhibit mutant p53 gain of function and consequently reduce the tumorigenic potential of cancer cells. A possible mechanism for transactivation of the c-myc gene by mutant p53 is proposed.

Animals↗

[Effects of lead on neurone cells and distribution of calcium in rat brain].

OBJECTIVE: To study the relationship between blood lead levels and damage in neurone cells. METHODS: Young rats were fed with water containing 10 and 20 mg/L of lead for three months since the first day of their weaning. Lanthanum nitrate tracing, calcium cytochemical location technique and Golgi's stain were used to observe changes in rat brain tissues. RESULTS: There were no obvious changes in brain tissues of the low-dose group as its blood lead level reached 1.67 times high as that in control one. Permeability of neurone cells changed and distribution of calcium in plasmalemma increased and their cytoplasm disintegrated in part of the microtubule in the dendrites and axons of the neurones as its blood lead level in high-dose group reached 2.46 times high as that in control one. CONCLUSION: It is possible that pathological changes found in this study provide a basis for the decrease in cognitive function caused by lead during their middle brain development in rats.

Animals↗

[Human cytomegalovirus infection and congenital malformation].

OBJECTIVE: To study the relationship between intrauterine cytomegalovirus (HCMV) infection and congenital malformation, and to determine the distribution of tissues infected. METHODS: Autopsy samples of 41 infants with congenital malformation and 19 infants with normal appearances were studied. Using polymerase chain reaction (PCR) technique the paraffin embedded specimens of main organs were examined for HCMV infection. In-situ hybridization (ISH) was performed in some of the PCR positive tissues in order to define the distribution of HCMV DNA. RESULTS: 19 of the 41 infants (46.34%) with congenital defects were HCMV positive, while 1 in 19 (5.26%) were positive in the control group, and there was significant difference between the 2 groups (P < 0.05), 20.46% (35/171) of the fetal organ samples were HCMV DNA positive in the malformation group, but only 1 out of 78 samples (1.28%%) was positive in the pulmonary tissue of the control group. More malformations of the digestive system were presented in HCMV infected babies but no statistical significant difference when compared with other systems. Brain tissue had the highest HCMV infection rates (41.37%, 12/29), which was significantly higher than other organs. By ISH technique HCMV DNA was found only in 6 out of 17 PCR positive samples, and they were located at neurons, neurogliocytes, epithelium and interstitial cells of the kidney, and epithelial cells of pulmonary alveolar. CONCLUSION: There are strong correlation between HCMV infection and congenital malformation, and brain is more susceptible to HCMV. By combining PCR and ISH, both sensitivity and distribution of HCMV could be obtained.

Abnormalities, Multiple↗

[Study on gene of YRRM in azoospermia].

OBJECTIVE: To detect the abnormal YRRM gene in azoospermia and to explore the pattern of YRRM gene in Chinese men. METHODS: With the special primer for YRRM, the YRRM gene was analyzed using the PCR method. Extracting the testis total RNA, we performed the RT-PCR. The part of YRRM gene was sequenced. RESULTS: No amplification band of YRRM gene was noted in 4 of 74 Chinese men with azoospermia (5.4%). The YRRM gene was obviously expressed in the testis of man and showed a 500 bp cDNA fragment. The cDNA and genomic DNA were different because the intron. We found that Chinese people only have YRRM1 pattern of gene, and the sequence of YRRM gene of Chinese men shows that the composition of the nucleotide is same as YRRM1 gene. CONCLUSION: These cases of abnormal YRRM gene may result in male infertility, YRRM gene and azoospermia is the YRRM1 gene is polymouphase of racial.

Adult↗

Visco-supplementation therapy in internal derangement of temporomandibular joint.

OBJECTIVE: To study if visco-supplementation therapy is useful to the internal derangement (ID) of temporomandibular joint (TMJ). METHODS: Sixty-three ID cases (69 TMJs) were studied by visco-supplementation therapy. The upper and/or lower articular cavities were irrigated with 5 ml normal saline and injected 0.3-1.0 ml 1% hyaluronate (HA) into articular cavity. If the symptoms of the disease still existed one week later, the therapy should be repeated for 1-2 times, once a week. The control group cases were injected 1 ml 2% lidocaine instead of HA. 8 other TMJs of 6 ID cases and 2 normal cadavers were studied with scanning electron microscopy (SEM) and light microscopy (LM). RESULTS: The visco-supplement therapy was useful to ID patients. The difference between the test group and control group had statistical significance (chi 2 = 6.6535, P < 0.01). SEM and LM showed that the condyle, disc and bilaminar region in ID were degenerated or destroyed. CONCLUSIONS: The friction between the articular surfaces in ID was increased and the bilaminar region could not retract the disc as in healthy TMJ. The visco-supplementation therapy can decrease the friction and resume the normal rheology of the diseased TMJs.

Adolescent↗

[Determination of gastric emptying time of functional dyspepsia and clinical study on therapeutic effect of Weihuigui decoction on functional dyspepsia].

OBJECTIVE: To observe the gastric emptying time (GET) of and the therapeutic effect of Weihuigui Decoction (WHGD) upon functional dyspepsia (FD). METHODS: GET of 64 FD patients and 20 healthy volunteers was measured by real time ultrasonography. The measurements were performed at fasting, 0, 10, 20, 30, 40 and 50 min after drinking water, the area of gastric antrum, internal diameter of the section of anterior posterior walls in corpus ventriculi fundus junction region, intitating time of gastric contraction and contractive times in 2 min were recorded. Twenty patients selected randomly were treated with WHGD 100 ml, three times a day, for 2 weeks consecutively, to observe the improvement of clinical effect and gastric emptying. RESULTS: GET was delayed in 66% of 64 FD patients as compared with that of control, and it was related with gastric contraction initiating time and contraction times in 2 min. WHGD could improve the clinical symptoms and GET of FD patients. CONCLUSION: WHGD has obvious therapeutic effect in treating FD.

Adolescent↗

[The application of spiral-CT three-dimensional reconstruction in chronic otitis media].

OBJECTIVE: To study the use of spiral-CT three-dimensional reconstruction in chronic otitis media. METHODS: The images of spiral-CT three-dimensional reconstruction (SCT-3DI) and surgical findings in 22 ears with chronic otitis media were compared. RESULTS: The lesions showed in SCT-3DI were in accord with those seen in the operation. There were no bone erosion in the 3 ears with simple type otitis media, and the 19 ears with cholesteatoma showed: abnormal soft-tissue and bony erosion in the tympanic cavity and antrum; dislocation and disruption of the ossicular chain; and showed disruption of sigmoid sinus plate, tegmen tympani, semicircular canal and facial nerve canal in severe cases. CONCLUSION: The spiral-CT has more superiority over traditional-CT in diagnosis of lesions in chronic otitis media before operation.

Adult↗

[The correlation between P-glycoprotein and multidrug resistance of squamous carcinoma in oral and maxillofacial region].

OBJECTIVE: To study the mechanism of drug resistance of oral carcinoma to chemotherapy. METHODS: 40 cases of squamous carcinoma in the oral and maxillofacial region were examined for the multidrug resistance gene product P-glycoprotein using a monoclonal antibody MRK16. RESULTS: P-glycoprotein was detected in 62.5% of the sample. P-glycoprotein expression was related to the chemotherapy and the degree of differentiation. P-glycoprotein expression was higher in post-chemotherapy group than in unchemotherapy group (P < 0.05). Well differentiated tumors expressed P-glycoprotein more frequently (P < 0.05). P-glycoprotein expression was compared with clinic response to chemotherapy. The accuracy rate of prediction is 75%. CONCLUSION: P-glycoprotein plays an important role in mechanism of multidrug resistance of squamous carcinoma in the oral and maxillofacial region.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Pathological changes of viscera after brain death: an experimental study].

In order to study the viscera changes after brain death while the function of the heart and lung was sustained artificially, 34 cats were used and divided into three groups. The results showed that pathological changes of viscera (heart, lung, liver and kidney) developed, including 1. ischemic cardiomyopathy, endocardiac hemorrhage, focal necrosis, mitochondria and microfilament destruction. 2. pulmonary congestion, edema and parenchymal inflammation. 3. ischemic lesions in the central band of hepatic lobular and ischemic lesions in renal proximal convoluted tubule.

Animals↗

[Diagnosis of Falciparum malaria by immunochromatographic test].

AIM: To evaluate the applicability of rapid immunochromatographic test(ICT) for diagnosing falciparum malaria in outpatient clinics in endemic area. METHODS: With thick blood smear method as control, ICT was used for the detection of P. falciparum. RESULTS: The sensitivity and specificity of ICT in detecting P. falciparum was 94.7% and 90.3%, respectively. No cross-reaction with P. vivax was found (P > 0.05). CONCLUSION: ICT is much more rapid and simple than thick blood smear method for the diagnosis of falciparum malaria, and can be applied in the outpatient clinics in endemic area.

Adolescent↗

Solution structure of the aminofluorene-intercalated conformer of the syn [AF]-C8-dG adduct opposite a--2 deletion site in the NarI hot spot sequence context.

This paper addresses structural issues related to the capacity of aminofluorene [AF] for frameshift mutations of the -2 type on C8 covalent adduct formation at the G3 site in the d(C-G1-G2-C-G3-C-C) NarI hot spot sequence. This problem has been approached from a combined NMR and relaxation matrix analysis computational structural study of the [AF]dG adduct in the d(C-G-G-C-[AF]G-C-C).d(G-G-C-C-G) sequence context at the 12/10-mer adduct level (designated [AF]dG.del(-2) 12/10-mer). The proton spectra of this system are of exceptional quality and are consistent with the formation of an AF-intercalated conformer with the modified guanine in a syn alignment displaced along with the 5'-flanking cytosine residue into the major groove. The solution structure has been determined by initially incorporating intramolecular and intermolecular proton-proton distances defined by lower and upper bound deduced from NOESY spectra as restraints in molecular mechanics computations in torsion angle space and subsequently refined through restrainted molecular dynamics calculations based on a NOE distance and intensity refinement protocol. Strikingly, the [AF]dG.del(-2) 12/10-mer duplex adopts only one of two potential AF-intercalation alignments for the [AF]dG adduct opposite the -2 deletion site in the NarI sequence context with the extrusion of the dC-[AF]dG step favored completely over extrusion of the [AF]dG-dC step at the lesion site. This polarity establishes that the structural perturbation extends 5' rather than 3' to the [AF]dG lesion site in the adduct duplex. This structure of the [AF]dG adduct opposite a -2 deletion site shows distinct differences with conclusions reported on the alignment of the related acetylaminofluorene [AAF]dG adduct opposite a -2 deletion site in the identical NarI sequence context [Milhe, C., Fuchs, R. P. P., and Lefevre, J. F. (1996) Eur. J. Biochem. 235, 120-127]. In that study, qualitative NMR data without computational analysis were employed to conclude that the extrusion at the lesion site occurs at the [AAF]dG-dC step for the AAF-intercalated conformer of the adduct duplex. The structure of the [AF]dG adduct opposite a -2 deletion site determined in our group provides molecular insights into the architecture of extended slipped mutagenic intermediates involving aromatic amine intercalation and base-displaced syn modified guanines in AF and, by analogy, AAF-induced mutagenesis in the NarI hot spot sequence context.

Acetoxyacetylaminofluorene↗

Solution structure of the aminofluorene-stacked conformer of the syn [AF]-C8-dG adduct positioned at a template-primer junction.

A solution structural study has been undertaken on the aminofluorene-C8-dG ([AF]dG) adduct located at a single strand-double strand d(A1-A2-C3-[AF]G4-C5-T6-A7-C8-C9-A10-T11-C12-C13).d (G14-G15-A16-T17-G18-G19-T20-A 21-G22) 13/9-mer junction (designated [AF]dG 13/9-mer) using proton-proton distance and intensity restraints derived from NMR data in combination with a computational protocol, which includes intensity refinement. This single strand-double strand junction models one arm of a replication fork composed of a 13-mer template strand, which contains the [AF]dG modification site, and a 9-mer primer strand, which has been elongated up to, but not including, the modified guanine. The NMR data establish that the duplex segment retains a minimally perturbed B-DNA conformation including Watson-Crick hydrogen-bonding at the junctional dC5.dG22 base pair. The NMR spectra are consistent with the guanine ring of the [AF]dG4 adduct adopting a syn glycosidic torsion angle and being displaced into the major groove with the adjacent dC3 residue displaced into the minor groove. Such a base displacement of the modified guanine is accompanied by stacking of one face of the fluorene ring of [AF]dG4 with the dC5.dG22 base pair, while the other face of the flourene ring is stacked with the purine ring of the nonadjacent dA2 residue in the intensity-refined solution structures of the [AF]dG 13/9-mer. A comparison of structural features of the C8-[AF]dG adduct (this study) with those of the (+)-trans-anti-N2-[BP]dG adduct [Cosman et al. (1995) Biochemistry 34, 15334-15350] in the same 13/9-mer junctional sequence context has identified common features associated with the alignment of the modified guanine adducts at the template-primer junction. Thus, despite differences in the covalent linkage site for the C8-[AF]dG and (+)-trans-anti-N2-[BP]dG adducts, one face of the aromatic ring of the carcinogen stacks over the junctional base pair and in so doing displaces the modified guanine in a syn alignment into the major groove. These results lend credence to earlier proposals that such an adduct alignment may represent a common mutagenic conformer at a template-primer junction associated with a replication fork.

Acetoxyacetylaminofluorene↗

Cholinergic control of nerve growth factor in adult rats: evidence from cortical cholinergic deafferentation and chronic drug treatment.

It is well documented that nerve growth factor (NGF) plays an important role in maintaining functions of cholinergic basal forebrain neurons. In the present study, we tested the hypothesis that cholinergic activity controls NGF levels in cholinoceptive neurons of the cerebral cortex and hippocampus. To address that question, we used both cholinergic deafferentation of cerebral cortex and hippocampus by cholinergic immunolesion with 192IgG-saporin and chronic pharmacological treatment of sham-treated and immunolesioned rats with the cholinergic agonist pilocarpine and the cholinergic antagonist scopolamine. We observed an increase in NGF protein levels in the cortex and hippocampus after cholinergic immunolesions and also after muscarinic receptor blockade by chronic intracerebroventricular scopolamine infusion in sham-treated rats after 2 weeks. There was no further increase in the accumulation of NGF after scopolamine treatment of immunolesioned rats. Chronic infusion of pilocarpine had no effect on cortical and hippocampal NGF protein levels in sham-treated rats. In rats with cholinergic immunolesions, however, pilocarpine did prevent the lesion-induced accumulation of NGF. There was no effect of cholinergic lesion and drug treatment on cortical or hippocampal NGF mRNA levels, consistent with the importance of NGF retrograde transport as opposed to its de novo synthesis. This study provides strong evidence for the hypothesis that there is cholinergic control of cortical and hippocampal NGF protein but not mRNA levels in adult rats.

Animals↗

[Prostacyclin participates in regulation of hypoxic and high CO2 cerebrovascular tension].

By using prostacyclin synthetase inhibitor-indomethacin, the effects of prostacyclin in the presence of endothelial cell on hypoxia- and high CO2-induced vasodilatation were studied in newborn calf basilar artery strips. The results showed that indomethacin had no effects on cerebrovascular tension, but attenuated the hypoxia- and high CO2-induced vasodilatation. After destroying the endothelial cell, the cerebral vascular dilatation was decreased, and indomethacin had no obvious effect on the vascular tension. These results suggest that both prostacyclin and endothelial cell are involved in hypoxia- and high CO2-induced vasodilatation and the former is derived from endothelial cell.

Animals↗

[The inhibitory effect of hydroprednisolone on tumor necrosis factor in rabbits' temporomandibular joint disturbance syndrome].

In order to study the mechanism of hydroprednisolone for temporomandibular joint disturbance syndrome (TMJDS), 12 white rabbits were injected TNF into the rabbits' right TMJDS for 2 to 3 times, 90,000 u each time, then another drug, 2 mg hydroprednisolone, was injected into these TMJDS again. The rabbits were killed after 8 to 18 days and the TMJDS were examined by microscope. We found the articular tissues only destroyed slightly and sometimes the cartilages were nearly normal. So, the study suggested that hydroprednisolone can reduce the destruction of TNF on rabbit's TMJ obviously. This may be the cause why hydroprednisolone is useful to TMJDS.

Animals↗