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Biomedical subjects

Li Zhang

Publications and source records attributed to Li Zhang.

At least 685 records · Page 38Linked to original sources
PubMed2002

Complexation of ytterbium to human transferrin and its uptake by K562 cells.

There is an increasing interest in the use of lanthanides in medicine. However, the mechanism of their accumulation in cells is not well understood. Lanthanide cations are similar to ferric ions with regard to transferrin binding, suggesting transferrin-receptor mediated transport is possible; however, this has not yet been confirmed. In order to clarify this mechanism, we investigated the binding of Yb3+ to apotransferrin by UV-Vis spectroscopy and stopped-flow spectrophotometry, and found that Yb3+ binds to apotransferrin at the specific iron sites in the presence of bicarbonate. The apparent binding constants of these sites showed that the affinity of Yb3+ is lower than that of Fe3+and binding of Yb3+ in the N-lobe is kinetically favored while the C-lobe is thermodynamically favored. The first Yb3+ bound to the C-lobe quantitatively with a Yb/apotransferrin molar ratio of < 1, whereas the binding to the other site is weaker and approaches completeness by a higher molar ratio only. As demonstrated by 1H NMR spectra, Yb3+ binding disturbed the conformation of apotransferrin in a manner similar to Fe3+. Flow cytometric studies on the uptake of fluorescein isothiocyanate labeled Yb3+-bound transferrin species by K562 cells showed that they bind to the cell receptors. Laser scanning confocal microscopic studies with fluorescein isothiocyanate labeled Yb3+-bound transferrin and propidium iodide labeled DNA and RNA in cells indicated that the Yb3+ entered the cells. The Yb3+-transferrin complex inhibited the uptake of the fluorescein labeled ferric-saturated transferrin (Fe2-transferrin) complex into K562 cells. The results demonstrate that the complex of Yb3+-transferrin complex was recognized by the transferrin receptor and that the transferrin-receptor-mediated mechanism is a possible pathway for Yb3+ accumulation in cells.

Binding, Competitive↗
PubMed2002

Sample survey of drug-resistant tuberculosis in Henan, China, 1996.

BACKGROUND: There is little reliable data on the global drug resistance to tuberculosis (TB) as most of the existing data is based upon biased samples, is not standardized or was obtained using poor techniques. For this reason, the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) developed a global project on anti-TB drug resistance surveillance (DRS) in 1994. China joined this project in 1995 and the province of Henan was selected as the first site for collection of representative samples to survey the prevalence of drug-resistant TB. METHODOLOGY: Standard drug susceptibility testing by the proportion method against streptomycin (S), isoniazid (H), rifampicin (R), and ethambutol (E) was performed with Mycobacterium tuberculosis isolated from 916 new cases and 456 previously treated cases. Treatment outcome of these patients has been evaluated according to the regimens and drug susceptibility patterns. RESULTS: Drug resistance among new cases to any drug was found to be 43.0% and any resistance: S, 32.5%; H, 31.0%; R, 20.7%; and E, 10.3%. Drug resistance among previously treated cases to any drug was 68.2% and any resistance: S, 52.2%; H, 49.3%; R, 48.3%; and E, 20.4%. The cure rate for new cases was 43.3% and 29.4% for previously treated cases. The poor cure rate resulted mainly from a high defaulter rate. CONCLUSION: Drug-resistant TB was found to be highly prevalent in Henan and the cure rate remained poor. The results strongly indicated that Henan should take immediate action to improve the cure rate of patients through expansion of the introduction of the directly observed treatment short-course strategy.

Adult↗
PubMed2002

Human fibroblasts transfected with cytomegalovirus immediate-early genes show increased MHC class I expression and are targets for natural killer cell-mediated cytotoxicity.

Natural killer (NK) cells are an important line of defense against viral infections, such as those caused by cytomegalovirus (CMV), but in the context of solid organ transplantation NK responses to CMV-infected graft cells might be deleterious to the graft survival. To gain a better understanding of NK responses to CMV-infected human lung fibroblasts (HLF), we transfected HLF with a plasmid expressing CMV immediate-early (IE) genes under the control of the CMV major IE promoter and compared major histocompatibility complex (MHC) class I expression and NK-mediated lysis of transfected cells, CMV-infected cells, and appropriate controls. HLF transfected with CMV IE genes showed increased MHC Class I expression and triggered NK-mediated cytotoxicity at the same level as CMV-infected HLF and at significantly higher levels than mock-infected or mock-transfected controls. Transfection of CMV genes provides an experimental model for molecular studies of CMV- and allograft-specific cell-mediated immunity and modulation.

Adult↗
PubMed2002

An examination of heme action in gene expression: heme and heme deficiency affect the expression of diverse genes in erythroid k562 and neuronal PC12 cells.

The aim of this study was to identify key genes whose expression is altered by heme and heme deficiency in the human erythroleukemia K562 cells and in the NGF-induced rat pheochromocytoma neuronal PC12 cells, respectively. By quantitative RT-PCR, Northern blotting, and Western blotting analyses, we found that the expression of the CDK inhibitors p18 and p21 was upregulated at the early and late stages of heme-induced erythroid differentiation of K562 cells, respectively, while the expression of cyclin D1 was downregulated. Data from succinyl acetone and desferrioxamine treatments suggest that these effects of heme in K562 cells were specific. Further, by microarray expression analysis, we found that inhibition of heme synthesis by succinyl acetone in NGF-induced PC12 cells drastically altered the expression of several groups of important neuronal genes, including the structural genes encoding neurofilament proteins and synaptic vesicle proteins, regulatory genes encoding signaling components beta-arrestin and p38 MAPK, and stress-response genes encoding hsp70. These results show that heme and heme deficiency affect the expression of diverse genes in a cell-type specific manner in mammalian cells, and that heme, although needed at different levels, is critical for both erythropoiesis and neurogenesis. These studies provide insights into how heme may act to control diverse regulatory processes in mammals.

Actins↗
PubMed2002

Correlation of VEGF and angiopoietin expression with disruption of blood-brain barrier and angiogenesis after focal cerebral ischemia.

In an effort to elucidate the molecular mechanisms underlying cerebral vascular alteration after stroke, the authors measured the spatial and temporal profiles of blood-brain barrier (BBB) leakage, angiogenesis, vascular endothelial growth factor (VEGF), associated receptors, and angiopoietins and receptors after embolic stroke in the rat. Two to four hours after onset of ischemia, VEGF mRNA increased, whereas angiopoietin 1 (Ang 1) mRNA decreased. Three-dimensional immunofluorescent analysis revealed spatial coincidence between increases of VEGF immunoreactivity and BBB leakage in the ischemic core. Two to 28 days after the onset of stroke, increased expression of VEGF/VEGF receptors and Ang/Tie2 was detected at the boundary of the ischemic lesion. Concurrently, enlarged and thin-walled vessels were detected at the boundary of the ischemic lesion, and these vessels developed into smaller vessels via sprouting and intussusception. Three-dimensional quantitative analysis of cerebral vessels at the boundary zone 14 days after ischemia revealed a significant (P < 0.05) increase in numbers of vessels (n = 365) compared with numbers (n = 66) in the homologous tissue of the contralateral hemisphere. Furthermore, capillaries in the penumbra had a significantly smaller diameter (4.8 +/- 2.0 microm) than capillaries (5.4 +/- 1.5 microm) in the homologous regions of the contralateral hemisphere. Together, these data suggest that acute alteration of VEGF and Ang 1 in the ischemic core may mediate BBB leakage, whereas upregulation of VEGF/VEGF receptors and Ang/Tie2 at the boundary zone may regulate neovascularization in ischemic brain.

Angiopoietin-1↗
PubMed2002

Magnetic resonance imaging characterization of hemorrhagic transformation of embolic stroke in the rat.

Intracranial hemorrhage is a critical factor when considering efficacy and safety of thrombolytic intervention after thromboembolic stroke. This study tested whether magnetic resonance imaging could identify tissue for hemorrhagic transformation after the onset of embolic stroke. Rats subjected to embolic stroke with and without recombinant tissue-type plasmogen activator (rt-PA) treatment were followed-up with magnetic resonance imaging using the inverse of the apparent forward transfer rate for magnetization transfer (k(inv)), gadolinium-chelate contrast-enhanced magnetic resonance imaging, and diffusion-, perfusion-, and T2-weighted imaging. Rats with embolic stroke either were treated with rt-PA 1 (n = 16) or 4 hours (n = 13) after stroke onset or were not treated (n = 15). From these groups, at total of 17 rats had intracerebral hemorrhage. Tissue progressing to hemorrhage and adjacent to the site of hemorrhage was analyzed to identify magnetic resonance imaging markers that characterize hemorrhagic transformation. The parameter maps of k(inv) and contrast-enhanced magnetic resonance imaging showed greater sensitivity in the detection of tissue destined for hemorrhagic transformation compared with the apparent diffusion coefficient of water (ADCw) and CBF. In tissue not destined to undergo hemorrhagic transformation, k(inv) maps and contrast-enhanced magnetic resonance imaging exhibited small increases in k(inv) and contrast-enhanced magnetic resonance imaging signal intensity in the area encompassing the territory supplied by the middle cerebral artery. In contrast, large increases in k(inv) and in signal intensity in the contrast-enhanced magnetic resonance images were detected in the region where gross hemorrhage was confirmed histologically. The values of k(inv), T2, and signal intensity in the contrast-enhanced magnetic resonance images were significantly higher in the region destined for hemorrhagic transformation (k(inv), P < or = 0.033 3-24 hours after embolization; T2, P < or = 0.037 24-48 hours; contrast-enhanced magnetic resonance imaging, P < 0.05 4-7 hours) compared with the nonhemorrhagic transformation ischemic region or in the contralateral homologous regions after onset of ischemia. Of these methods, k(inv) shows the most sensitivity in the detection of hemorrhagic transformation soon after embolization. The authors' data suggest that k(inv) and contrast-enhanced magnetic resonance imaging are potentially important methodologies for detecting tissue destined for hemorrhagic transformation.

Animals↗
PubMed2002

SmeC, an outer membrane multidrug efflux protein of Stenotrophomonas maltophilia.

A homologue of the mexAB-oprM multidrug efflux operon of Pseudomonas aeruginosa, smeABC, was cloned from Stenotrophomonas maltophilia by using, as a probe, a PCR product amplified from this organism with primers based on the mexB sequence. The smeABC genes were hyperexpressed in a mutant strain displaying resistance to several antimicrobials, including aminoglycosides, beta-lactams, and fluoroquinolones. Deletions in smeC but not smeB compromised this resistance, suggesting that SmeC contributed to the multidrug resistance of the mutant as part of another, as-yet-unidentified multidrug efflux system. Consistent with SmeC functioning independently of SmeAB, a promoter activity was identified upstream of smeC. Upstream of the smeABC genes, a putative two-gene operon, smeSR, encoding homologues of bacterial two-component regulatory systems was identified. The cloned smeR gene activated expression of a smeA-lacZ fusion, indicating that SmeR positively regulates expression of the smeABC genes. Consistent with this, the multidrug resistance of the SmeABC-hyperexpressing mutant was compromised by deletion of smeR. Intriguingly, SmeC expression in S. maltophilia paralleled a beta-lactamase activity provided by a C-terminally truncated L2 enzyme, which was apparently responsible for the beta-lactam resistance of the SmeABC-hyperexpressing mutant. This represents the first report of coregulation of an efflux resistance determinant and a beta-lactamase.

Bacterial Outer Membrane Proteins↗
PubMed2002

Genomic association/linkage of sodium lithium countertransport in CEPH pedigrees.

Little is known about genetic determinants explaining variation in the erythrocyte sodium-lithium countertransport (SLC), an intermediate phenotype of essential hypertension. We characterized the SLC in immortalized lymphoblasts and showed that its behavior is similar to that of erythrocyte SLC. We then performed association and linkage analyses of the SLC in immortalized lymphoblasts from 5 large pedigrees from the Center d'Etude du Polymorphisme Humain (CEPH) genomics repository. The results of these analyses showed that a number of genomic regions harboring genes involved in glutathione metabolism might explain variations in SLC activity. These findings support evidence that thiol groups play a central role in SLC activity.

Alleles↗
PubMed2002

Sildenafil (Viagra) induces neurogenesis and promotes functional recovery after stroke in rats.

BACKGROUND AND PURPOSE: We tested the hypothesis that sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, promotes functional recovery and neurogenesis after stroke. METHODS: Male Wistar rats were subjected to embolic middle cerebral artery occlusion. Sildenafil (Viagra) was administered orally for 7 consecutive days starting 2 or 24 hours after stroke onset at doses of 2 or 5 mg/kg per day. Ischemic rats administered the same volume of tap water were used as a control group. Functional outcome tests (foot-fault, adhesive removal) were performed. Rats were killed 28 days after stroke for analysis of infarct volume and newly generated cells within the subventricular zone and the dentate gyrus. Brain cGMP levels, expression of PDE5, and localized cerebral blood flow were measured in additional rats. RESULTS: Treatment with sildenafil significantly (P<0.05) enhanced neurological recovery in all tests performed. There was no significant difference of infarct volume among the experimental groups. Treatment with sildenafil significantly (P<0.05) increased numbers of bromodeoxyuridine-immunoreactive cells in the subventricular zone and the dentate gyrus and numbers of immature neurons, as indicated by betaIII-tubulin (TuJ1) immunoreactivity in the ipsilateral subventricular zone and striatum. The cortical levels of cGMP significantly increased after administration of sildenafil, and PDE5 mRNA was present in both nonischemic and ischemic brain. CONCLUSIONS: Sildenafil increases brain levels of cGMP, evokes neurogenesis, and reduces neurological deficits when given to rats 2 or 24 hours after stroke. These data suggest that this drug that is presently in the clinic for sexual dysfunction may have a role in promoting recovery from stroke.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2002

A novel allele in the promoter of the hepatic lipase is associated with increased concentration of HDL-C and decreased promoter activity.

Hepatic lipase (HL) is a lipolytic enzyme involved in the metabolism of plasma lipoproteins, especially HDLs. Association of the polymorphisms in the promoter region of the LIPC gene to post-heparin plasma HL activity and the plasma HDL-C concentration has been investigated thoroughly, but to date little is known about this in the Chinese. In the present study, we analyzed the polymorphisms in the promoter region of LIPC gene in Chinese patients with coronary artery disease (CAD) using denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. As the result, a novel single nucleotide polymorphism -586T-to-C was identified and no linkage of this variant with other polymorphisms in the promoter was found. Compared with the nonsymptomatic control subjects, excess of carriers of the -586T/C substitution were detected in the CAD patients (43% vs. 31%, chi(2) = 4.597, degree of freedom = 2, P = 0.032). The -586C allele carriers in the CAD patients had a significantly higher HDL-C level than the noncarriers (1.13 +/- 0.24 mmol/l vs. 0.91 +/- 0.14 mmol/l, P < 0.05). To test the functionality of this substitution, luciferase-reporter assays was performed in HepG2 cells. Promoter activity of the -586C construct was decreased 2-fold than the -586T construct. Our studies suggest that a T-to-C substitution at -586 of the LIPC promoter is associated with a lowered HL activity and that this variation may contribute to the increased plasma HDL-C concentration in the Chinese.

Adult↗
PubMed2002

A nitroimidazole derivative, PR-350, enhances the killing of pancreatic cancer cells exposed to high-dose irradiation under hypoxia.

The radiosensitizing effects of PR-350, a nitroimidazole derivative, were examined concerning the cell killing of human pancreatic cancer cell lines exposed to high doses of gamma-ray irradiation in vitro. The percentages of dead cells were analyzed with a multiwell plate reader to measure the fluorescence intensity of propidium iodide before and after a digitonin treatment. The sensitizing effect of PR-350 on cell killing by high-dose irradiation was confirmed by time-course, dose-dependency, and microscopic observations. In five of seven pancreatic cancer cell lines in which the number of dead cells was determined 5 days after 30 Gy irradiation in the presence of PR-350, the number was significantly increased under hypoxic conditions, but not under aerobic conditions. The selective radiosensitive effect of PR-350 on hypoxic cells was also confirmed by flow cytometry. The results indicate that PR-350 can enhance the killing of pancreatic cancer cells by high-dose irradiation under hypoxia, which supports its clinical radiosensitizing effects when administered during intraoperative irradiation to pancreatic cancer.

Cell Death↗
PubMed2002

Pharmacokinetics of multiple intravenous instillation of levofloxacin in Chinese healthy subjects.

AIM: To study the pharmacokinetics of multiple doses intravenous infusion of levofloxacin instillation in Chinese healthy volunteers. METHODS: Intravenous infusion of levofloxacin instillation 200 mg within 60 min was given to 10 male healthy volunteers for 7 d, on d 1 and d 7, once-daily, from 2-6 d twice-daily dosing. The concentrations of levofloxacin in serum and urine were assayed by HPLC. RESULTS: The main pharmacokinetic parameters af ter the first dosing were as follows: Cmax was (2.4+/-0.4) mg/L; AUC0- was (16.1 +/- 1.4) mg . h . L-1; T1/2beta was (6.3 +/- 0.3) h. The concentration in serum reached steady state within 72 h. The main parameters after the last dosing were as follows: Cssmax was (2.9 +/- 0.4) mg/L; Cssmin was (0.71 +/- 0.19) mg/L; Cav was (1.40 +/- 0.29) mg/L; AUCss0-12 was (17 +/- 3) mg . h . L-1; T1/2beta was (6.2 +/- 0.8) h. The 24-h cumulative urinary excretion rate was (88 +/- 5) %. From the calculation, the cumulative rate was 1.20; the fluctuation index was 1.30. The difference of T1/2beta and AUC between the first dosing and the last dosing was not significant, and the elimination rate of levofloxacin was not changed after multiple dosing. No clear adverse events were noted during this study. CONCLUSION: There was no accumulation of drug after the repeated intravenous infusion with 200 mg levofloxacin instillation for 7 d.

Adult↗
PubMed2002

[The change in sensitivity of methicillin-resistant Staphylococcus aureus to vancomycin].

OBJECTIVE: To determine the shift of susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) isolates to vancomycin in recent years. METHODS: Antimicrobial susceptibility was determined by disk diffusion test (K-B method). The t-test was used to compare the mean diameters of zone of inhibition. RESULTS: The clinical isolates of MRSA from 1994 to 2000 were 218, 187, 292, 237, 351, 886 and 652 in number respectively. The mean diameters (mm) of the inhibition zone of MRSA isolates each year were 19.9, 19.1, 18.6, 17.4, 18.4, 18.2 and 17.8. Comparison of the diameters of the inhibition zone of MRSA isolates (K-B method) showed that the mean diameter of the inhibition zone from the 652 MRSA isolates in 2000 was much less than that of the 218 MRSA isolates in 1994 and the difference was significant (P < 0.001). The resistant rates to chloramphenicol, ciprofloxacin, erythromycin, gentamicin, tetracycline and trimethoprim/sulfamethoxazole were 44.0%, 73.7%, 89.1%, 65.7%, 61.0% and 67.0%. CONCLUSION: Our observation demonstrated that the susceptibility of MRSA to vancomycin gradually decreased from 1994 to 2000. It is important to monitor the antimicrobial susceptibility of Staphylococcus aureus to vancomycin.

Anti-Bacterial Agents↗
PubMed2002

[Direct transsphenoidal pituitary adenoma resection under endoscope].

OBJECTIVE: To discuss the primary experience and possibility of direct transsphenoidal pituitary adenoma resection under endoscopic assistance. METHODS: From March 2000 to March 2001, 22 patients with pituitary adenoma were treated by direct transsphenoidal pituitary adenoma surgery under endoscope. During direct transsphenoidal approach, no incision of the nasal mucosa was made without the dissection of the nasal septum and median nasal conchae. Under endoscopic assistance, the anterior wall of the sphnoidal sinus and sellae base was opened directly and adenoma resection was performed. RESULTS: All the patients were followed up for 1 approximately 12 months. The increased hormone level in 17 patients were decreased to normal postoperatively. By postoperative MRI detection, adenomas in 15 patients were removed completely, but part of the adenomas were left in the carvernous sinuses in 7 patients. Temporary diabetes insipidus was observed in 4 patients. CONCLUSIONS: The direct transsphenoidal approach in pituitary adenoma resection under endoscopic assistance is time saving, and safe, with good exposure of operative field. The injury to the patient and postoperative reaction are less. The effects were satisfactory without severe complications.

Adenoma↗
PubMed2002

Pathological morphology alteration of the splanchnic vascular wall in portal hypertensive patients.

OBJECTIVE: To investigate the pathological morphology alteration of the splanchnic vascular wall in portal hypertensive patients. METHODS: Splenic arteries, veins and gastric coronary veins from portal hypertensive patients (n = 50) were removed during esophagogastric devascularization with splenectomy and were observed under optic and electron microscopes. The expression of iNOS in the splenic artery wall was analysed with immunohistochemistry. RESULTS: The internal elastic membrane and medial elastic fibers of the splenic artery wall were broken and degenerated. Atrophy, apoptosis and phenotypic changes were seen in smooth muscle cells of splenic arteries. Positive staining for iNOS was seen in the cytoplasm of smooth muscle cells and iNOS activity was elevated compared with the non-cirrhotic patients (P < 0.01). In the splenic and gastric coronary veins of cirrhotic patients, we found proliferative intima, extensive thrombi adhering to the venous wall, mimicked arteriosclerosis plaques accompanied with hypertrophy of smooth muscle cells, and thickened muscle fibers of veins with increase in extracellular matrix. CONCLUSION: Portal hypertension may be complicated by splanchnic arterial and venous vasculopathy. There may be an interactive relationship among portal hypertension, splanchnic hyperdynamic disturbances and splanchnic vasculopathy in the pathogenesis of portal hypertension.

Adult↗
PubMed2002

Relationship between a novel polymorphism of lipoprotein lipase gene and coronary heart disease.

OBJECTIVE: To investigate polymorphisms in the gene for lipoprotein lipase (LPL) in Chinese populations with coronary heart disease (CHD) and to inquire into the relationship between these polymorphisms in LPL gene and CHD. METHODS: Genomic DNA was extracted from patients with CHD and normal control subjects using a salting out method. The entire coding region and flanking sequences of all coding exons of the LPL gene were amplified by PCR technique and PCR products were detected by denaturing high-performance liquid chromatography (DHPLC) and sequenced with a dideoxy terminal termination method. RESULTS: A novel polymorphic site, G830A, that is within the fifth exon of the LPL gene was found. The 192 codon CGA was changed into CAA and resulted in the substitution of glutamine for arginine. Between the control and CHD groups, chi-square test showed no significant difference in the frequencies of the A/A genotype and A allele (P > 0.05). However, the frequencies of A/A genotype and A allele (0.653 and 0.786) in CHD patients with high plasma triglyceride/lowed plasma high density lipoprotein cholesterol were higher than those (0.415 and 0.642) in CHD patients without hyperlipidemia (P < 0.05). CONCLUSION: No direct association was found between the LPL Arg192-->Gln substitution polymorphism and CHD, but there is a significant positive correlation between the A/A genotype of the LPL gene and CHD associated with high triglyceride/lowed high density lipoprotein cholesterol. This study may provide new data for exploring the molecular mechanism of CHD.

Alleles↗
PubMed2002

[Repair of the facial tissue defects with reversed narrow pedicle lateral maxillocervical fasciocutaneous flap].

OBJECTIVE: To introduce a method of repairing facial tissue defects caused by various factors. METHODS: The reverse narrow pedicle lateral maxillocervical fasciocutaneous flap was designed with its pedicle located in front of auricle. The size of the flaps ranged from 5 cm x 6 cm to 10 cm x 11 cm. The length and width of the pedicle ranged 2 cm-5 cm and 1 cm-1.5 cm. RESULTS: This fasciocutaneous flap was used in 21 cases. All flaps survived except 1 flap showing distal skin necrosis. CONCLUSION: This fasciocutaneous flap didn't include any major blood vessel. The ratio of the pedicle width to flap length broke that of traditional flap and was reverse transfer. The transposition of the narrow pedicle flap was easy. The postoperative appearance (color, texture, cosmetic aspect) was satisfactory. This method was a new design and was ideal for large facial tissue defect repair.

Adolescent↗