Biomedical subjects

H Zhu

Publications and source records attributed to H Zhu.

At least 109 records · Page 6Linked to original sources

PubMed2001

Opiate withdrawal during development: are NMDA receptors indispensable?

Despite decades of research, the mechanisms that underlie opiate tolerance, dependence and withdrawal remain elusive. Evidence accumulated over the past ten years suggests that the NMDA receptor plays a central role in mediating the neuroplasticity induced by chronic opiate administration in adult animals. Yet, during ontogeny, the NMDA receptor complex undergoes qualitative developmental changes, which renders some of the basic assumptions for a role of the NMDA receptor in opiate withdrawal invalid in infants. Recent data indicate that NMDA receptor antagonists are not effective in blocking morphine tolerance, dependence and withdrawal in the neonatal rat. Roles for other glutamate receptor types (e.g. metabotropic glutamate receptors) have also been proposed recently. In this article, the latest evidence that characterizes the dynamic roles of glutamate receptors in these phenomena during ontogeny will be discussed.

Aging↗

PubMed2001

Further evidence for a role of NMDA receptors in the locus coeruleus in the expression of withdrawal syndrome from opioids.

To examine a role of N-methyl-D-aspartate (NMDA) receptors in the locus coeruleus (LC) in the expression of the withdrawal signs from opioids, rats were continuously infused with morphine (a mu-opioid agonist, 26 nmol/microl per h) or butorphanol (a mu/delta/kappa-mixed opioid agonist, 26 nmol/microl per h) intracerebroventricularly (i.c.v.) through osmotic minipumps for 3 days. An LC injection of NMDA (0.1 and 1 nmol/5 microl) induced withdrawal signs in opioid-dependent animals. However, it did not precipitate any abnormal behaviors in saline-treated control rats. The expression of the withdrawal signs precipitated by NMDA (1 nmol/5 microl), glutamate (10 nmol/5 microl), or naloxone (an opioid antagonist, 24 nmol/5 microl) was completely blocked by pretreatment with a NMDA antagonist, MK-801 (5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptan-5,10-imine), 0.1 mg/kg, i.p. In animals that had been infused with opioids in the same manner, naloxone (48 nmol/5 microl, i.c.v.) precipitated withdrawal signs and increased extracellular glutamate levels in the LC of opioid-dependent rats measured by in vivo microdialysis method. Pretreatment with MK-801, however, did not affect the increases of glutamate levels in the LC. These results further demonstrate that the expression of opioid withdrawal induced by an expeditious release of glutamate in the LC region of opioid-dependent animals might be mainly mediated by the postsynaptic NMDA receptors.

Animals↗

PubMed2001

Risk factors and child mortality among the Miao in Yunnan, Southwest China.

Environmental factors and the lifestyle of communities in developing countries as in the industrialized world have a great deal to do with their health status. This study carried out among the Miao people of southeastern Yunnan province in Southwest China has demonstrated important links between child mortality (one indicator of health status) and specific risk factors. These include lifestyle variables such as geographic mobility, the age of weaning and religious belief. In addition, the use of available health care facilities was another explanatory variable. Perhaps surprisingly, a history of tuberculosis seemed also to be empirically related to the presence or absence of child mortality. Although it was impossible to show a significant statistical relationship between traditional practices and child mortality from the study's database, the authors have observed qualitatively that birthing customs play an important role in explaining the perinatal component of child mortality. These various relationships shed some light on potential areas for intervention with a view to reducing the levels of child mortality among minority peoples in China and elsewhere.

China↗

PubMed2001

Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound.

The purpose of this study was to investigate the pathologic changes of extracorporeal ablation of human malignant tumors with high-intensity focused ultrasound (HIFU). HIFU treatment was performed in the 164 patients with liver cancer, breast cancer, malignant bone tumor, soft tissue sarcoma and other malignant tumors at focal peak intensities from 5000 W x cm(-2) to 20,000 W x cm(-2), with operating frequencies of 0.8 to 3.2 MHz. To explore the pathologic impact of extracorporeal HIFU, 30 patients with malignant carcinoma underwent surgical removal after HIFU treatment. Pathologic findings showed that the treated tissues demonstrated homogeneous coagulative necrosis with an irreversible tumor cell death and severe damage to tumor blood vessels at the level of microsvasculature within the HIFU-targeted region. Thermolesions to intervening tissue were never observed. The treated region had a sharp border comprising only several cell layers between the treated and untreated areas. The repair of lesions had the processes of necrotic tissue absorption and granulation tissue replacement. It is concluded that extracorporeal treatment of human solid malignancies with HIFU could be safe, effective and feasible. As a noninvasive therapy, HIFU would be used clinically to treat patients with solid malignancies.

Bone Neoplasms↗

PubMed2001

Age-related increase in mitochondrial superoxide generation in the testosterone-producing cells of Brown Norway rat testes: relationship to reduced steroidogenic function?

Aging in Brown Norway rats is accompanied by the reduced production of testosterone by the Leydig cells, the testicular cells responsible for synthesizing and secreting this essential steroid. As yet, the mechanism by which Leydig cell steroidogenesis is reduced is unknown. Herein we assess the production of mitochondrial reactive oxygen species by intact Leydig cells isolated from the testes of young and old rats. To this end, Leydig cells were incubated with lucigenin (bis-N-methylacridinium nitrate), a probe that enters cells, localizes to mitochondria, and yields a significant chemiluminescent response following its reaction with intramitochondrial superoxide. Leydig cells from old rats elicited significantly greater lucigenin-derived chemiluminescence (LDCL) than those from young rats. Electron microscopic stereological analysis revealed that the absolute volume of mitochondria in the old cells was reduced from that in the young. These results, taken together, suggest that there are age-related changes in the production of reactive oxygen species by the mitochondria of Leydig cells, with those of old Leydig cells producing significantly greater levels than those of young Leydig cells. The results are consistent with the proposal that mitochondrial-derived reactive oxygen may play a role in the irreversible decline in the ability of old Leydig cells to produce testosterone.

Aging↗

PubMed2001

Effect of RF coil excitation on field inhomogeneity at ultra high fields: a field optimized TEM resonator.

In this work, computational methods were utilized to optimize the field produced by the transverse electromagnetic (TEM) resonator in the presence of the human head at 8 Tesla. Optimization was achieved through the use of the classical finite difference time domain (FDTD) method and a TEM resonator loaded with an anatomically detailed human head model with a resolution of 2 mm x 2 mm x 2 mm. The head model was developed from 3D MR images. To account for the electromagnetic interactions between the coil and the tissue, the coil and the head were treated as a single system at all the steps of the model including, numerical tuning and excitation. In addition to 2, 3, 4, 6, and 10-port excitations, an antenna array concept was utilized by driving all the possible ports (24) of a 24-strut TEM resonator. The results show that significant improvement in the circularly polarized component of the transverse magnetic field could be obtained when using multiple ports and variable phase and fixed magnitude, or variable phase and variable magnitude excitations.

Electromagnetic Fields↗

PubMed2001

The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent cell death.

Here, we investigate the mechanism and function of LKB1, a Ser/Thr kinase mutated in Peutz-Jegher syndrome (PJS). We demonstrate that LKB1 physically associates with p53 and regulates specific p53-dependent apoptosis pathways. LKB1 protein is present in both the cytoplasm and nucleus of living cells and translocates to mitochondria during apoptosis. In vivo, LKB1 is highly upregulated in pyknotic intestinal epithelial cells. In contrast, polyps arising in Peutz-Jegher patients are devoid of LKB1 staining and have reduced numbers of apoptotic cells. We propose that a deficiency in apoptosis is a key factor in the formation of multiple benign intestinal polyps in PJS patients, and possibly for the subsequent development of malignant tumors in these patients.

AMP-Activated Protein Kinase Kinases↗

PubMed2001

Protein arrays and microarrays.

In the past, studies of protein activities have focused on studying a single protein at a time, which is often time-consuming and expensive. Recently, with the sequencing of entire genomes, large-scale proteome analysis has begun. Arrays of proteins have been used for the determination of subcellular localization, analysis of protein-protein interactions and biochemical analysis of protein function. New protein-microarray technologies have been introduced that enable the high-throughput analysis of protein activities. These have the potential to revolutionize the analysis of entire proteomes.

Animals↗

PubMed2001

In vitro binding of an orally active platinum antitumor drug, JM216 to metallothionein.

The in vitro binding of an orally active anticancer drug JM216 to metallothionein is firstly investigated in this paper. It is revealed that a redox reaction following a substitution reaction from JM216 with rabbit liver Zn7MT-II is presented. The reaction feature, the metal binding stoichiometry and the oxidation states of platinum and sulfur in the products are studied by UV-visible, chromatography and X-ray photoelectron spectroscopy methods. Parts of MT are oxidized to precipitate products with intra and intermolecular CyS-SCy disulfides linkages. Pt(IV) is reduced to its Pt(II) counterpart. And the reduced Pt(II) replace the metal ions in native MTs. Meanwhile it can also cause the dimerization of MT. Increasing the reaction ratio of JM216 to MT leads to a concomitant increase in the apparent yield of the precipitate and dimeric products and the elevation of the binding stoichiometry of Pt to the protein. Based on the experimental data, the reaction mechanism between JM216 and Zn7MT-II in vitro are discussed.

Administration, Oral↗

PubMed2001

Cytotoxic effects of antiproliferative agents on human retinal glial cells in vitro.

PURPOSE: Proliferative vitreoretinopathy (PVR) is characterized by the formation of cellular membranes on the detached retina and also in the vitreous. Glial cells can be found in epiretinal and subretinal membranes from eyes with PVR, proliferative diabetic retinopathy (PDR), idiopathic macular pucker, uveitis and other diseases affecting the retina. Proliferation and contraction of glial cells appears to play a role in the pathogenesis of PVR. This study is designed to inspect the effectiveness of harringtonine, as well as colchicine, daunomycin and fluorouracil, against cellular proliferation of cultured human retinal glial cells that might be involved in the retinal and/or vitreous proliferation. METHODS: Cultures of human retinal glial cells were prepared using the enzyme digesting method. Cells that had been in culture for 2-5 passages were used in this study. Harringtonine (0.063 microg/ml approximately 2.0 microg/ml), colchicines (0.5 microg/ml approximately 16.0 microg/ml), daunomycin (0.1 microg/ml approximately 3.2 microg/ml) and 5-fluorouracil (0.5 microg/ml approximately 16.0 microg/ml) were added to cultures of human retinal glial cells and the proliferation rates of the cells were measured by the MTT method. RESULTS: Harringtonine at the dosage of 0.063 microg/ml induced suppression of cellular growth, but the changes were not statistically significant (p > 0.05). At a dosage ranging from 0.125 microg/ml to 2.0 microg/ml, harringtonine significantly suppressed cellular growth according to the test (p < 0.01). Likewise, other antiproliferative agents inhibited cellular growth significantly at a dosage from 1.0 microg/ml to 16.0 microg/ml (colchicine), 0.2 microg/ml to 3.2 microg/ml (daunomycin) and 1.0 microg/ml to 16.0 microg/ml (5-fluorouracil), but not at 0.5 microg/ml (colchicine), 0.1 microg/ml (daunomycin) and 0.5 microg/ml (5-fluorouracil). The ID50 were 0.33 microg/ml (harringtonine), 3.11 microg/ml (colchicine), 0.79 microg/ml (daunomycin) and 5.23 microg/ml (5-fluorouracil), respectively. CONCLUSIONS: Harringtonine was extremely effective in inhibiting human retinal glial cell proliferation, like other antiproliferative drugs such as colchicine, daunomycin and 5-fluorouracil. Harringtonine, therefore, may be a candidate for further studies regarding the treatment of experimental PVR.

Adult↗

PubMed2001

IL-18-stimulated GADD45 beta required in cytokine-induced, but not TCR-induced, IFN-gamma production.

Interleukin-12 (IL-12) and IL-18 induce synergistic transcription of interferon gamma (IFN-gamma) that is T cell receptor (TCR)-independent, not inhibited by cyclosporin A and requires new protein synthesis. To characterize this pathway, we screened for genes that are induced in IL-12- and IL-18-treated T helper type 1 cells. GADD45 beta, which activates mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase kinase 4 (MEKK4), was induced by IL-18 and augmented by IL-12. GADD45 beta expression in naïve CD4+ T cells activated p38 MAPK and selectively increased cytokine-induced, but not TCR-induced, IFN-gamma production. Kinase-inactive MEKK4 and inhibition of the p38 MAPK pathway both selectively inhibit cytokine-induced, but not TCR-induced, IFN-gamma production. Thus, the synergy between IL-12 and IL-18 may involve GADD45 beta induction, which can maintain the MEKK4 and p38 MAPK activation that is necessary for cytokine-induced, but not TCR-induced, IFN-gamma production.

Animals↗

PubMed2001

Analysis of HCV-IG isotype complexes by a novel immuno-capture RT-PCR method.

HCV can be present in the circulating blood either as a free virus or as a virion-immunoglobulin (Ig) complex. All isotypes of Igs may form the virus complexes, but it remains unclear what specific role of each Ig plays in the clearance of HCV. In the present study, we have combined immuno-capture and RT-PCR, and developed a quick double-specificity method for detecting and distinguishing different HCV-Ig complexes. We compared our new method, the immuno-capture RT-PCR (iRT-PCR), with the conventional RT-PCR (cRT-PCR) for the sensitivity of detecting HCV in 35 clinically diagnosed patients with HCV infection. The results showed that 31 patients were detected to be positive by using iRT-PCR, whereas 16 patients were positive with the use of cRT-PCR. HCV-IgM, HCV-IgG, HCV-IgA could separately be detected by iRT-PCR and their positive rates were 66.7%, 51.0%, 62.7%, respectively. HCV bound to antibody was a common feature of hepatitis C (HC) and 86.3% of patients were positive at least by one of the HCV-Ig tests. The patterns of HCV RNA constituents varied according to disease categories. In summary, iRT-PCR is a valuable method for analysis of the composition of the immune complexes, which may provide new and valuable insights into HCV pathogenesis.

Adolescent↗

PubMed2001

Serotype and adhesion of Pseudomonas aeruginosa isolated from contact lens wearers.

The purpose of the present study was to correlate the serotypes of Pseudomonas aeruginosa to the bacterial adhesion to contact lenses and human corneal epithelial cells. Twenty-three strains isolated from contact lens wearers were used for the study. The bacterial serotypes were examined with a P. aeruginosa antisera kit. The attachment of bacteria on contact lenses or human corneal epithelial cells was determined by counting the number of adhered bacteria after incubation of the bacteria with contact lenses or corneal epithelial cells. The 23 ocular isolates belonged to seven serotypes. Strains of serotypes I, G and E were the three dominant serogroups and were more adhesive to contact lenses compared with other groups of the bacteria. The bacterial serotypes and the clinical sequelae were not strongly related. These results indicate that the surface characteristics of bacterial serotypes are related to the bacterial adhesion to the surface, but the pathogenesis of the bacteria may result from multiple factors.

Bacterial Adhesion↗

PubMed2001

Production of N-acyl homoserine lactones by gram-negative bacteria isolated from contact lens wearers.

The purpose of this study was to investigate the production of N-acyl-homoserine lactone (AHL) signal molecules in ocular gram-negative bacteria. A total of 91 ocular strains isolated from contact lens adverse response patients and asymptomatic subjects were used in the study. These included Acinetobacter, Aeromonas hydrophila, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Pseudomonas aeruginosa, Serratia liquefaciens, Serratia marcescens, and Stenotrophomonas maltophilia. The biosensor strains Chromobacterium violaceum mutant CV026 and Agrobacterium tumefaciens A136 were used for detection of AHL signal molecules. The majority of A. hydrophila, P. aeruginosa, and S. liquefaciens strains produced more than one AHL molecule. Serratia marcescens strains were AHL positive only under detection of A136. The rest of the test species did not show any AHL production under the current detection system. These findings indicate that AHL-mediated quorum-sensing systems are present in some of the ocular bacteria, and the different signal molecules may be involved with the quorum-sensing pathway in the other bacterial species.

4-Butyrolactone↗

PubMed2001

Random amplified polymorphic DNA analysis of Acinetobacter species isolated from worn contact lenses.

The purpose of this study was to explore the genotypes of Acinetobacter species and to compare the genotypes and phenotypes of the Acinetobacter isolated from contact lens wearers. Nineteen strains were used in the study, 13 were isolated from patients experiencing an adverse response event, and six strains were isolated from asymptomatic contact lens wearers. Random amplified polymorphic DNA and phenotypic analyses were carried out using commercially available kits. Random amplified polymorphic DNA analysis showed a higher discrimination power compared with the phenotypic analysis. The test strains were loosely clustered into six genotypic groups with no definite relation to any clinical events. These results indicate that many genotypes of Acinetobacter can cause adverse responses, and the initial source of the microorganisms rather than their clinical sequelae may determine classification.

Acinetobacter↗

PubMed2001

The role of IL-1beta in the regulation of IL-8 and IL-6 in human corneal epithelial cells during Pseudomonas aeruginosa colonization.

PURPOSE: Recent studies have shown that the levels of interleukin (IL)-1beta, IL-6 and IL-8 are associated with the severity of infectious diseases. The purpose of this study was to investigate whether IL-1beta regulates the expression of IL-6 and IL-8 in human corneal epithelial cells during Pseudomonas aeruginosa colonization. METHODS: Confluent immortalized human corneal epithelial cells were challenged with P. aeruginosa 6294 in the presence of anti-human IL-1beta antibody or matched control antibody. The cells were also challenged with recombinant IL-1beta protein without bacterial colonization. Expression of IL-1beta, IL-6 and IL-8 mRNA and protein was detected by reverse transcription (RT)-PCR and by enzyme-linked immunosorbent assay (ELISA), respectively. IL-1beta localization was determined by immunohistochemistry. RESULTS: Human corneal epithelial cells expressed low levels of IL-1beta and high levels of IL-6 and IL-8 during P. aeruginosa colonization. Addition of IL-1beta Ab resulted in a significant decrease (P < 0.05) in IL-8 protein expression at 4 h, 8 h and 12 h. Addition of IL-1beta Ab reduced IL-6 protein expression at 8 h and increased IL-6 protein expression at 12 h. Addition of recombinant IL-1beta protein alone strongly stimulated the expression of IL-8 and IL-6. Immunohistochemical staining showed that IL-1beta protein was present both intracellularly and extracellularly in P. aeruginosa colonized cells. CONCLUSIONS: IL-1beta is able to modulate expression of both IL-6 and IL-8 at transcriptional and post-transcriptional levels in human corneal epithelial cells.

Cells, Cultured↗

PubMed2001

A new sesquiterpene lactone from Tsoongiodendron odorum Chun.

A new sesquiterpene lactone (1) was obtained from the cytotoxic fraction of 95% ethanol extract of root barks of Tsoongiodendron odorum Chun together with two known sesquiterpene lactones, costunolide (2) and parthenolide (3). The structure of 1 was elucidated as 5alpha, 6alpha, 7beta, 10beta- 11alpha, 13-dihydro-4(15)-eudesmene-12, 6-olide on the basis of chemical and spectral evidence including X-ray diffraction analysis. Costunolide showed cytotoxic activity against human leukemia (HL-60) cell line. Parthenolide showed promising cytotoxic activities in vitro against HCT-8, Bel-7402, SKOV3, KB, HELA and EJ cell lines. Also, the cytotoxic ethyl acetate fraction of ethanol extract of the root barks from which three chemical components were isolated showed promising cytotoxic activities in vitro against KB, BGC-823, Bel-7402, HCT-8, HL-60 cell lines.

Antineoplastic Agents, Phytogenic↗

PubMed2001

APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex.

In mitosis, the anaphase-promoting complex (APC) regulates the onset of sister-chromatid separation and exit from mitosis by mediating the ubiquitination and degradation of the securin protein and mitotic cyclins. With the use of a baculoviral expression system, we have reconstituted the ubiquitin ligase activity of human APC. In combination with Ubc4 or UbcH10, a heterodimeric complex of APC2 and APC11 is sufficient to catalyze the ubiquitination of human securin and cyclin B1. However, the minimal APC2/11 ubiquitin ligase module does not possess substrate specificity, because it also ubiquitinates the destruction box deletion mutants of securin and cyclin B1. Both APC11 and UbcH10 bind to the C-terminal cullin homology domain of APC2, whereas Ubc4 interacts with APC11 directly. Zn(2+)-binding and mutagenesis experiments indicate that APC11 binds Zn(2+) at a 1:3 M ratio. Unlike the two Zn(2+) ions of the canonical RING-finger motif, the third Zn(2+) ion of APC11 is not essential for its ligase activity. Surprisingly, with Ubc4 as the E2 enzyme, Zn(2+) ions alone are sufficient to catalyze the ubiquitination of cyclin B1. Therefore, the Zn(2+) ions of the RING finger family of ubiquitin ligases may be directly involved in catalysis.

Amino Acid Sequence↗