Biomedical subjects

Hong Zhang

Publications and source records attributed to Hong Zhang.

At least 361 records · Page 20Linked to original sources

PubMed2003

Synthesis, crystal structure, and photochromism of novel two-dimensional supramolecular networks based on Keggin-type polyoxoanion and lanthanide coordination cations.

Three new compounds [Ln(NMP)(4)(H(2)O)(4)][H(x)()GeMo(12)O(40)].2NMP.3H(2)O (Ln = Ce(IV) (1), Pr(IV) (2), x = 0; Ln = Nd(III) (3), x = 1; NMP = N-methyl-2-pyrrolidone) have been prepared in aqueous solution and characterized by elemental analyses, IR, UV-vis, and TG analyses. The single crystal X-ray diffraction shows that all three compounds are isostructural. In their structures, an interesting two-dimensional supramolecular network is constructed by the [GeMo(12)O(40)](4)(-) anion and [Ln(NMP)(4)(H(2)O)(4)](3+/4+) cation building blocks via hydrogen-bonding interactions, exhibiting the porous structure. Upon irradiation with UV light, the crystals of 1-3 show photochromic behavior.

Journal Article↗

PubMed2003

Differential control over postganglionic neurons in rat cardiac ganglia by NA and DmnX neurons: anatomical evidence.

In previous single-labeling experiments, we showed that neurons in the nucleus ambiguous (NA) and the dorsal moto nucleus of the vagus (DmnX) project to intrinsic cardiac ganglia. Neurons in these two motor nuclei differ significantly in the size of their projection fields, axon caliber, and endings in cardiac ganglia. These differences in NA and DmnX axon cardiac projections raise the question as to whether they target the same, distinct, or overlapping populations of cardiac principal neurons. To address this issue, we examined vagal terminals in cardiac ganglia and trace injection sites in the brain stem using two different anterograde t ace s 1,1-dioleyl-3,3,3,3-tetramethylindocarbocyanine methanesulfonate and 4-[4-(dihexadecylamino)-styryl]-N-methylpyridinium iodide] and confocal microscopy in male Sprague-Dawley rats. We found that 1) NA and DmnX neurons innervate the same cardiac ganglia, but these axons target separate subpopulations of principal neurons and 2) axons arising from neurons in the NA and DmnX in the contralateral sides of the brain stem enter the cardiac ganglionic plexus through separate bundles and preferentially innervate principal neurons near their entry regions, providing topographic mapping of vagal motor neurons in left and right brain stem vagal nuclei. Because the NA and DmnX project to distinct populations of cardiac principal neurons, we propose that they may play different roles in controlling cardiac function.

Animals↗

PubMed2003

Attenuation of baroreflex sensitivity after domoic acid lesion of the nucleus ambiguus of rats.

The nucleus ambiguus (NA) and the dorsal motor nucleus of the vagus (DmnX) innervate distinct populations of cardiac ganglionic principal neurons. This anatomic evidence suggests that these two nuclei play different roles (Cheng Z and Powley TL, Soc Neurosci Abstr 26: 1189, 2000). However, lesion of the DmnX does not attenuate baroreflex sensitivity (Cheng Z, Guo SZ, Lipton AJ, and Gozal D, J Neurosci 22: 3215-3226, 2002). The present study tested the functional role of the NA in baroreflex control of heart rate (HR). Domoic acid (DA) was injected into the left NA of Sprague-Dawley rats to lesion the NA. The neuronal loss was assessed using retrograde labeling and confocal microscopy. HR changes induced by phenylephrine and sodium nitroprusside administration and after electrical stimulation of the left vagal trunk were measured at 15 days, and HR responses to left NA microinjection of L-glutamate were determined at 180 days postlesion. Compared with vehicle injections, DA lesions significantly reduced the population of NA motor neurons by approximately 68% (P < 0.01) and attenuated baroreflex sensitivity by approximately 83% (P < 0.01) at 15 days. Similarly, electrical stimulation of the vagal trunk of DA-lesioned animals led to attenuated decreases in HR responses. NA neuronal counts were reduced by approximately 81% (P < 0.01) and mean HR responses to l-glutamate injection into the lesioned NA were attenuated by approximately 65% (P < 0.01) at 180 days. Therefore, the NA plays a major role in baroreflex control of HR, and the integrity of the NA is critically important for the normal baroreflex control. In addition, NA lesions produce long-term anatomic and functional dysfunction of the nucleus, and thus it may provide an useful model for functional assessment of respective roles of the NA and DmnX.

Animals↗

PubMed2003

Establishment of BMD reference plots and determination of peak BMD at multiple skeletal regions in mainland Chinese women and the diagnosis of osteoporosis.

Osteoporosis is a major public health problem, particularly in women. Bone mineral density (BMD) reference plot is a basic, and the peak BMD (PBMD) an important, parameter in the diagnosis of osteoporosis. In order to establish reference plots of BMD at multiple skeletal sites in Chinese women and improve the diagnostic accuracy for osteoporosis, we measured BMDs at several skeletal regions in 3,378 Chinese women, aged 5-96 years, using a dual-energy X-ray absorptiometry fan-beam bone densitometer. After determining that the cubic regression model best fit all skeletal regions, we utilized the curve-fitting to establish BMD reference plots and utilized the curve-fitting equation to calculate the highest BMDs at all skeletal regions using three different methods of calculation--actual PBMD (method A), PBMD of each 5-year age group (method B), and a cross-section of age (method C). When the three methods were compared, we found significant differences among them at the majority of skeletal regions studied. When we utilized these three methods to determine the prevalence of osteoporosis in 2,120 women aged 40 years and older, except for the Ward's triangle, we observed significant differences among them at all skeletal regions. In the present study, we established new BMD reference plots at multiple skeletal regions for women of mainland China. Our findings also indicate that curve-fitting equations can be employed to calculate actual PBMDs specific to individual regions, and that the use of different methods to calculate PBMD may have a significant impact on both PBMD and the diagnosis of osteoporosis. Therefore, we suggest that a standardized method be established to calculate site-specific PBMDs based on the peak values of best-fit reference curves in appropriate age groups.

Absorptiometry, Photon↗

PubMed2003

Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism.

Riboflavin kinase (RFK) is an essential enzyme catalyzing the phosphorylation of riboflavin (vitamin B(2)) in the presence of ATP and Mg(2+) to form the active cofactor FMN, which can be further converted to FAD. Previously, the crystal structures of RFKs from human and Schizosaccharomyces pombe have been determined in the apo form and in complex with MgADP. These structures revealed that RFK adopts a novel kinase fold and utilizes a unique nucleotide binding site. The structures of the flavin-bound RFK obtained by soaking pre-existing crystals were also reported. Because of crystal packing restraints, these flavin-bound RFK complexes adopt conformations nearly identical with that of corresponding flavin-free structures. Here we report the structure of human RFK cocrystallized with both MgADP and FMN. Drastic conformational changes associated with flavin binding are observed primarily at the so-called Flap I and Flap II loop regions. As a result, the bound FMN molecule now interacts with the enzyme extensively and is well-ordered. Residues from Flap II interact with Flap I and shield the FMN molecule from the solvent. The conformational changes in Flap I resulted in a new Mg(2+) coordination pattern in which a FMN phosphate oxygen and Asn36 side chain carbonyl are directly coordinating to the Mg(2+) ion. The proposed catalytic base Glu86 is well-positioned for activation of the O5' hydroxyl group of riboflavin for the phosphoryl transfer reaction. The structural data obtained so far on human and yeast RFK complexes provide a rationale for the ordered kinetic mechanism of RFK.

Crystallization↗

PubMed2003

Expression of Glut-1 and Glut-3 in untreated oral squamous cell carcinoma compared with FDG accumulation in a PET study.

Increased expression of glucose transporter-1 (Glut-1) and glucose transporter-3 (Glut-3) has been reported in many human cancers. The mechanism of glucose entry into oral squamous cell carcinoma (OSCC) remains unclear. In this study we investigated, in untreated human OSCC, the relationship between tumour fluorine-18 fluoro-2-deoxy-D-glucose (FDG) accumulation and the expression of Glut-1 and Glut-3, as well as the association between the expression of Glut-1 and of Glut-3. All patients underwent FDG positron emission tomography (PET) pre-operatively. Standardised uptake values (SUVs) were used for evaluation of tumour FDG uptake. Final diagnoses were established by histology. Immunohistochemical staining results were evaluated according to the percentage (%) of positive area, intensity and staining score. Tumour sections were stained by immunohistochemistry for Glut-1 and Glut-3. Glut-1 immunostaining revealed that 18 (94.7%) of the 19 tumours stained positively, while Glut-3 immunostaining yielded positive findings for 16 (84.2%) tumours. Overall, a relatively low level of agreement (36.8%) in the staining score was observed between Glut-1 and Glut-3 expression. No relationship was found between the staining pattern and tumour differentiation or T grade classification in either Glut-1 or Glut-3 immunostaining. Furthermore, no relationship was found between increased FDG SUV and tumour differentiation, but the former did correlate with T grade. In conclusion, high FDG uptake values were seen in OSCC with overexpression of Glut-1 and Glut-3. However, no significant correlation was found between FDG SUV and Glut-1 or Glut-3 expression.

Aged↗

PubMed2003

Downregulation of IRS-1 protein in thapsigargin-treated human prostate epithelial cells.

Thapsigargin treatment of cultured cells leads to an increase in the intracellular calcium concentration, activation of calpain, and, in some cell types, apoptosis. Using a human prostate epithelial cell line that undergoes apoptosis in the presence of thapsigargin, we find decreased levels of IRS-1 protein levels during apoptosis. Inhibition of calpain prevents this decrease in IRS-1 protein; however, inhibitors of caspases or the proteasome are ineffective in maintaining IRS-1 levels. In terms of IGF-I-related second messenger proteins, the effect of thapsigargin is specific for IRS-1 since the protein levels of IGF-I receptor beta-subunit, Akt, Erk, and Shc are not affected. In addition to preventing the reduction in IRS-1, treatment of cells with calpain inhibitor II prevents apoptosis in response to thapsigargin. Finally, IRS-1 and calpain can be identified in protein complexes isolated using IRS-1-specific antibodies, indicating that calpain can associate with either IRS-1 or one of the proteins present in protein complexes that contain IRS-1. In total, these results suggest that IRS-1 may be targeted for degradation by calpain during apoptosis.

Apoptosis↗

PubMed2003

Artemisinin derivatives bearing Mannich base group: synthesis and antimalarial activity.

Novel artemisinin derivatives bearing Mannich base group were prepared and tested for their antimalarial activity. These water-soluble artemisinin derivatives were more stable than sodium artesunate and few compounds were found to be more active against Plasmodium berghei in mice than artesunic acid by oral administration. Two most potent derivatives 17b and 17d were examined for their antimalarial activity against Plasmodium knowlesi in rhesus monkeys.

Animals↗

PubMed2003

Ultraviolet A and B differently induce intracellular protein expression in human skin melanocytes--a speculation of separate pathways in initiation of melanoma.

Ultraviolet (UV) irradiation has been involved in both initiation and promotion of carcinogenesis in melanoma. Alterations of cellular proliferation proteins, such as p73, Nup88, Id1 and p27 have been considered to play critical roles in melanoma development. However, the molecular mechanisms behind melanoma carcinogenesis are still poorly understood. In this study, we used human skin melanocytes as an experimental model system to investigate effects of UV irradiation on protein expression concerning cellular proliferation. The melanocytes prepared from human foreskin were separately exposed to various doses of UVA or UVB and post-cultivated for 24 or 48 h. Total proteins were isolated from the melanocytes, and expression of p73, Nup88, Id1, p27, bcl-2 and proliferating cell nuclear antigen (PCNA) proteins was examined by western blotting and immunocytochemistry. Results showed that expression of p73 and Nup88 was enhanced by UVA irradiation in a dose- and time-dependent manner. However, expression of Id1, p27, bcl-2 and PCNA proteins was not changed upon exposure to the UVA. Id1 and p27 proteins were over-expressed by exposure to UVB, but expression of p73, Nup88, bcl-2 and PCNA proteins was not changed by the UVB irradiation. The data suggested that UVA and UVB irradiation might lead to alterations of the different intracellular proteins. UVA enhanced protein expression concerning cell growth (p73 and Nup88) and UVB might over-express proteins concerning cellular proliferation (Id1 and p27). UVA and UVB may induce initiation of melanoma via separate intracellular pathways.

Adolescent↗

PubMed2003

Transcriptional activation of placental growth factor by the forkhead/winged helix transcription factor FoxD1.

Stromal-epithelial interactions play an important role in renal organogenesis. Expression of the forkhead/winged helix transcription factor FoxD1 (BF-2) is restricted to stromal cells in the embryonic renal cortex, but it mediates its effects on the adjacent ureteric bud and metanephric mesenchyme, which fail to grow and differentiate in BF-2 null mice. BF-2 is therefore likely to regulate transcription of factors secreted by stromal cells that modulate the differentiation of neighboring epithelial cells. Here, we used cells with inducible expression of BF-2, combined with microarray analysis, to identify Placental Growth Factor (PlGF), a Vascular Endothelial Growth Factor (VEGF) family member previously implicated in angiogenesis, as a downstream target of BF-2. BF-2 binds to a conserved HNF3beta site in the PlGF promoter and activates transcription. PlGF is precisely coexpressed with BF-2, both temporally and spatially, within the developing renal stroma, and it is completely absent in BF-2 null kidney stroma. Addition of PlGF to in vitro kidney organ cultures stimulates branching of the ureteric bud. Our observations indicate that PlGF is a direct and physiologically relevant transcriptional target of BF-2. The contribution of PlGF toward stromal signals that regulate epithelial differentiation suggests novel functions for a growth factor previously implicated in reactive angiogenesis.

Animals↗

PubMed2003

The expression and functional characterization of ABCG2 in brain endothelial cells and vessels.

Delivery of drugs to the brain is impeded by the activity of efflux pumps expressed by endothelial cells of brain vasculature. The ATP binding cassette (ABC) transporters, among which ABCB1/MDR1 P-glycoprotein and ABCC1/multidrug resistance-associated protein 1 are expressed in brain endothelial cells, participate in drug efflux properties of the blood-brain barrier (BBB). Searches of the EST (expressed sequence tags) database with the conserved ABC domain, conducted to identify other ABC transporters expressed in the BBB, recovered 15 ABC transporter sequences expressed in human brain cDNA libraries. One of these sequences, identical to ABCG2, was highly expressed in cultured human cerebromicrovascular endothelial cells and human brain tissue at both mRNA and protein levels. Overexpression of human ABCG2 in immortalized rat brain endothelial cells resulted in enhanced polarized abluminal to luminal transport of various substrates tested in the in vitro BBB model. Brain vessels extracted from tissue sections of nonmalignant human brain and glioblastoma tumors by laser capture microdissection microscopy and analyzed by real-time polymerase chain reaction showed higher expression of ABCG2 relative to ABCB1/MDR1 and ABCC1/MRP1. ABCG2 was up-regulated in both glioblastoma vessels and parenchymal tissue. These studies suggest a role for brain endothelial ABCG2 transporter in modulating drug delivery to the brain and in conferring drug resistance to glioblastomas.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2003

Transition from spiral waves to defect-mediated turbulence induced by gradient effects in a reaction-diffusion system.

The transition from spiral waves to defect-mediated turbulence was studied in a spatial open reactor using Belousov-Zhabotinsky reaction. The experimental results show a new mechanism of the transition from spirals to spatiotemporal chaos, in which the gradient effects in the three-dimensional system are essential. The transition scenario consists of two stages: first, the effects of gradients in the third dimension cause a splitting of the spiral tip and a deletion of certain wave segments, generating new wave sources; second, the waves sent by the new wave sources undergo a backfire instability, and the back waves are laterally unstable. As a result, defects are automatically generated and fill all over the system. The result of numerical simulation using the FitzHugh-Nagumo model essentially agrees with the experimental observation.

Journal Article↗

PubMed2003

Suppression of spiral waves and spatiotemporal chaos by generating target waves in excitable media.

A method for suppressing spiral waves and spatiotemporal chaos in excitable media is proposed. Applying suitable periodic force to a single point, we can successfully suppress spiral waves as well as spatiotemporal chaos by generating target waves. After we turn off the external force, target waves finally disappear and the whole system which was in the state of spiral wave or spatiotemporal chaos goes to the spatially homogeneous steady state. It is shown that our control method is not sensitively model dependent. It works for a model for catalytic CO oxidation on platinum as well as for a model for cardiac muscle.

Journal Article↗

PubMed2003

Administration of dendritic cells transduced with antisense oligodeoxyribonucleotides targeting CD80 or CD86 prolongs allograft survival.

BACKGROUND: The expression of costimulatory molecules on antigen-presenting cells is crucial in determining T-cell immune responses. We examined the effects of transduction with high-affinity antisense oligodeoxyribonucleotides (ODNs) designed to target the mRNA of CD80 or CD86 on the phenotype and function of dendritic cells (DCs). MATERIALS AND METHODS: DCs were propagated from C57BL/10 (B10; H2b) bone marrow cells in granulocyte macrophage-colony stimulating factor and interleukin (IL)-4, and transduced with anti-CD80 or anti-CD86 antisense ODNs (base-mismatched ODNs as controls). The effect of antisense ODN on phenotype was examined by flow cytometry. The allostimulatory function of DCs was assessed by mixed leukocyte reaction and cytotoxic activity in vitro, and the influence on allograft survival was assessed in vivo. RESULTS: ODNs were effectively incorporated by DCs, which were enhanced by the presence of lipofectamine. Antisense ODNs targeting CD80 or CD86 mRNA specifically suppressed the expression of CD80 or CD86 in DCs and inhibited their capacity to elicit the proliferative responses, donor-specific cytotoxic T-lymphocyte activity in C3H (H2k) spleen T cells. This was associated with decreased IL-2, but elevated IL-4 production, and an increase in T-cell apoptosis. In contrast with the administration of control DCs into C3H recipients that exacerbated rejection of B10 cardiac allografts, injection of DCs transduced with anti-CD80 or CD86 antisense ODN significantly prolonged the survival of heart allografts. CONCLUSION: Transduction with antisense ODN targeting CD80 or CD86mRNA is a feasible and effective approach to modify DCs that renders them tolerogenic by inducing T-cell hyporesponsiveness and apoptosis. This may lead to the development of new therapeutic strategies in transplantation.

Animals↗

PubMed2003

SPAM1 (PH-20) protein and mRNA expression in the epididymides of humans and macaques: utilizing laser microdissection/RT-PCR.

BACKGROUND: The Sperm Adhesion Molecule 1 (SPAM1) is an important sperm surface hyaluronidase with at least three functions in mammalian fertilization. Previously our laboratory reported that in the mouse, in addition to its expression in the testis, Spam1 is synthesized in the epididymis where it is found in membranous vesicles in the principal cells of the epithelium in all three regions. Since SPAM1 is widely conserved among mammals the aim of the study was to determine if its expression pattern in the epididymis is conserved in rodents and primates. METHODS: We used laser microdissection (LM)/RT-PCR on frozen and paraffin-embedded epididymal sections of humans (n = 3) and macaques (n = 2) as well as in situ transcript hybridization to determine if transcripts are present in the epididymal epithelium. Western analysis and immunohistochemistry were used to detect and confirm the protein expression, and hyaluronic acid substrate gel electrophoresis analyzed its hyaluronidase activity. An in silico analysis of the proximal promoter of SPAM1 was also performed to identify relevant putative transcription binding sites for the androgen receptor. RESULTS: We demonstrate that mRNA unique to SPAM1 is present in the principal cells of the epididymal epithelium in all individuals of both species studied. SPAM1 protein is present in all three regions of the epididymis, as well as the vas deferens, and is localized similarly to the transcripts. SPAM1 was shown to have hyaluronidase activity at pH 7.0. In the proximal promoter of SPAM1 were uncovered putative epididymal transcription factor binding sites including androgen receptor elements (AREs), consistent with epididymal expression. CONCLUSIONS: These findings allow us to conclude that epididymal SPAM1 is conserved in at least two mammalian classes, rodents and primates. This conservation of expression suggests that the protein is likely to play an important function, possibly in sperm maturation.

Adult↗

PubMed2003

Adenosine inhibits activation-induced T cell expression of CD2 and CD28 co-stimulatory molecules: role of interleukin-2 and cyclic AMP signaling pathways.

Adenosine is an immunosuppressive molecule that is associated with the microenvironment of solid tumors. Mouse T cells activated with anti-CD3 antibody in the presence of adenosine with or without coformycin (to prevent adenosine breakdown by adenosine deaminase) exhibited decreased tyrosine phosphorylation of some intracellular proteins and were inhibited in their ability to proliferate and synthesize interleukin (IL)-2. In addition, adenosine interfered with activation-induced expression of the co-stimulatory molecules CD2 and CD28. Activation-induced CD2 and CD28 expression was also diminished when T cells were activated in the presence of anti-IL-2 and anti-CD25 antibodies to neutralize IL-2 bioactivity. Collectively, these data suggest that CD2 and CD28 up-regulation following T cell activation is IL-2-dependent; and that adenosine inhibits activation-induced T cell expression of CD2 and CD28 by interfering with IL-2-dependent signaling. The inhibitory effect of adenosine on activation-induced CD2 and CD28 expression could not be attributed to cyclic AMP (cAMP) accumulation resulting from the stimulation of adenylyl cyclase-coupled adenosine receptors, even though cAMP at concentrations much higher than those generated following adenosine stimulation was inhibitory for both CD2 and CD28 expression. We conclude that adenosine interferes with IL-2-dependent T cell expression of co-stimulatory molecules via a mechanism that does not involve the accumulation of intracellular cAMP.

Adenosine↗

PubMed2003

Antisense oligonucleotide inhibition of Bcl-xL and Bid expression in liver regulates responses in a mouse model of Fas-induced fulminant hepatitis.

Activation of the cell-surface receptor Fas can lead to apoptosis in parenchymal cells in the liver, and if severe enough, result in fulminant hepatic failure and animal death. In the present study, we have examined the roles played by the Bcl-2 family members Bcl-xL and Bid in regulating this response. To do this, we have developed chemically modified 2'-O-(2-methoxy) ethyl antisense inhibitors of both Bid and Bcl-xL expression. In Balb/c mice, dosing with these antisense oligonucleotides reduced expression of the targeted mRNA by greater than 80% in the liver. This reduction was highly dependent upon oligonucleotide sequence and oligonucleotide dose. Reduction of Bcl-xL expression resulted in a potentiation of Fas-mediated apoptosis in liver and significant increase of the lethality of Fas-mediated fulminant hepatitis (p < 0.0001). In contrast, reduction of Bid expression protected the animals against Fas-mediated fulminant hepatitis and death (p < 0.0001). Simultaneous dosing of mice with Bcl-xL and Bid-targeting antisense oligonucleotides resulted in an inhibition of expression of both targeted proteins and protection of the animals from Fas-mediated apoptosis. These results demonstrate, for the first time, the role of Bcl-xL in regulating responses to proapoptotic Fas signaling in mouse liver. In addition, this is the first reported example demonstrating the ability of antisense inhibitors to reduce expression of multiple proteins in animals by simultaneous dosing.

Animals↗

PubMed2003

Socioeconomic factors in cancer in Sweden.

It is well known that certain cancers have shown clustering in socioeconomic groups, but limited data are available on recent results and time trends in such clustering. We determined standardized incidence ratios (SIR) for cancer, adjusted for age, period, region, parity and age at first childbirth among men and women in 6 socioeconomic groups based on the Swedish Family-Cancer Database. Persons had to be identified with the same socioeconomic status in the census of years 1960 and 1970, or of years 1960, 1970 and 1980; the comparison group was all people according to the same censuses. Cancers were followed from years 1970 to 1998 or from 1980 to 1998. Both increased and decreased SIRs were found, and a consistent pattern emerged, although the overall SIRs for cancer did not differ much, the lowest being for farmers (0.85) and the highest for professional men (1.07) and women (1.11). At individual sites, manual workers were at risk of tobacco-, alcohol- and occupation- and human papilloma virus-related cancers and at a decreased risk at most other cancers. Manual workers and farmers showed an excess of stomach cancer; professionals had an excess of melanoma and squamous cell skin cancer. Male and female SIRs correlated highly for manual and blue-collar workers and for professionals. The overall population-attributable fraction for selected sites was 16.7% for men and 10.9% for women and it was highest, over 50%, for lung cancer in both genders.

Agricultural Workers' Diseases↗