Search PubMed⌕ Search

Biomedical subjects

Hong Zhang

Publications and source records attributed to Hong Zhang.

At least 307 records · Page 17Linked to original sources
PubMed2004

Affinity ultrafiltration of DNA topoisomerases-targeted compounds determined with HPLC/ESI-MS for drug candidate screening.

A method of screening assay is demonstrated. The approach is based on the affinity of antitumor candidates for topoisomerases. In this method, antitumor candidates are fished out using topoisomerases as targets. Traditional analysis of complex compounds typically encounters signal suppression due to the relatively low concentrations, but enzyme-affinity screening for the active compounds can effectively concentrate the desired analysts into a small volume of high concentration. Active compounds are separated from non-affinity compounds by ultrafiltration. The molecules-enzymes complexes that are retained on the filter are subsequently separated by acidification to obtain the topoisomerases-affinity compounds for analysis on High Performance Liquid Chromatography coupled with electrospray ionization mass spectrometric detection (ESI-MS). This enzyme-affinity based screening assay provides a highly specific and efficient method that can directly screen, identify, and acquire drug candidates thus improving the accuracy and speed of high-throughput screening activities.

Chromatography, High Pressure Liquid↗
PubMed2004

Effects of skeletal size of the lumbar spine on areal bone density, volumetric bone density, and the diagnosis of osteoporosis in postmenopausal women in China.

To understand the effects of skeletal size of the lumbar spine on areal bone mineral density (aBMD), volumetric bone mineral density (vBMD), and the diagnosis of osteoporosis in postmenopausal women, we measured the projected bone area, bone mineral content (BMC), aBMD, and vBMD at the anteroposterior and lateral lumbar spines in a population of 1081 postmenopausal Chinese women, 42 to 86 years of age. The results indicated that, at the anteroposterior and lateral lumbar spine, there were significant positive correlations between bone area and both BMC ( r = 0.606; P = 0.000 and r = 0.610; P = 0.000) and aBMD ( r = 0.270; P = 0.000 and r = 0.182; P = 0.000), but not vBMD ( r = -0.055; P = 0.000 and r = 0.000; P = 0.929). When bone area at the anteroposterior spine changed by +/-1 SD, the BMC, aBMD, and vBMD correspondingly changed by 28.2%, 10.1%, and 1.69% on the basis of their respective means. When a variation of +/-1 SD was observed in bone area at the lateral spine, BMC and aBMD, correspondingly changed by 25.9% and 6.18% on the basis of their respective means, while vBMD indicated no change. Through comparisons among large-, intermediate-, and small-bone area groups, significant differences were found in the means of subjects' heights, weights, BMC, and vBMD at the anteroposterior and lateral lumbar spines, as well as in the detection rates of osteoporosis by aBMD ( P = 0.000). Detection rates of osteoporosis by aBMD at the anteroposterior spine and by aBMD at the lateral spine, and by vBMD were 44.1%, 55.5%, and 49.7%, respectively, in the total population; 31.4%, 41.7%, and 53.7%, respectively, in the large-bone area group; 43.3%, 55.9%, and 50.5%, respectively, in the intermediate-bone area group; and 61.7%, 70.0%, and 42.5%, respectively, in the small-bone area group. No significant differences were found in the detection rates of osteoporosis by vBMD among the groups. The results of multiple linear regression revealed that the major factors influencing skeletal size and aBMD of the lumbar spine were height and weight. Therefore, in menopausal women of the same ethnic group and age, the skeletal size of the lumbar spine would have significant influence upon aBMD and the diagnosis of osteoporosis, i.e., the larger the spinal size, the greater the aBMD and the lower the osteoporosis detection rate, while, conversely, the smaller the skeletal size, the smaller the aBMD and the higher the osteoporosis detection rate. When we use aBMD of the lumbar spine to diagnose osteoporosis in a population with different body sizes, we need to take this body size difference into account. When we use vBMD to diagnose osteoporosis, the effect of body size on BMD will diminish.

Adult↗
PubMed2004

Determination of age-specific bone mineral density and comparison of diagnosis and prevalence of primary osteoporosis in Chinese women based on both Chinese and World Health Organization criteria.

The aim of this study was to determine age-specific bone mineral density (BMD) at various skeletal regions in a native Chinese reference population, and to explore the differences in the diagnosis of primary osteoporosis and estimated prevalence of osteoporosis based on both Chinese criteria (BMD of subjects, 25% lower than the peak BMD) and WHO criteria (BMD of subjects, 2.5 SD [T-score < or = -2.5] lower than the young adult mean [YAM]). There were 3,406 subjects in our female reference population, ranging in age from 10 to 90 years. A dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) was used to measure the BMD in subjects at the posteroanterior (PA) spine (L1-L4), supine lateral spine (L2-L4 including areal BMD [aBMD] and volumetric BMD [vBMD]), hip (including femoral neck and total hip), and radius + ulna ultradistal (R + UUD) of the forearm. Cross-sectional data analysis in stratified 5-year age intervals revealed that the peak BMD (PBMD) at various skeletal regions occurred within the age range of 30-44 years, with PBMD at the lateral spine and femoral neck occurring at 30-34 years, posteroanterior spine and total hip at 35-39 years, and ultradistal forearm at 35-44 years. The reference values of BMD (PBMD) calculated using Chinese criteria for the diagnosis of primary osteoporosis were significantly higher than the young adult mean (YAM) using WHO criteria for all skeletal regions except for the total hip, at a range of 0.9%-3.8% higher. The BMD cutoff values using Chinese criteria for the diagnosis of osteoporosis were 3.7%-10.9% higher than those using WHO criteria for various skeletal regions. The prevalence rate of primary osteoporosis according to Chinese criteria in subjects ranging from 50 to 90 years was 41.5% at the PA spine, 53.9% at the lateral spine, 34.2% at the femoral neck, 30.7% for total hip, and 51.4% at R + UUD; while according to WHO criteria, this rate was 32.1% at the PA spine, 34.9% at the lateral spine, 16.3% at the femoral neck, 18.9% for total hip, and 45.2% at R + UUD. The prevalence of primary osteoporosis according to both criteria varied with the age and skeletal region of the subjects. The prevalence of primary osteoporosis using Chinese criteria, compared with WHO criteria was 31% higher at the lumbar spine, 109% higher at the femoral neck, and 14% higher at the ultradistal forearm. In conclusion, PBMD occurs in the age range of 30-44 years in native Chinese females. The BMD reference values, BMD cutoff values, and prevalence of primary osteoporosis determined by Chinese criteria are all higher than those determined by the WHO criteria; thus, the application of Chinese criteria may overestimate the number of patients with primary osteoporosis.

Adolescent↗
PubMed2004

Expression and secretion of rat SPAM1(2B1 or PH-20) in the epididymis: role of testicular lumicrine factors.

Rat sperm surface antigen Sperm Adhesion Molecule1, SPAM1 (a.k.a. 2B1 or PH-20) is a plasma membrane-bound glycoprotein with hyaluronidase activity and putative roles during fertilization. Previously the antigen was thought to be testis-specific but recently it has been shown to be synthesized in the epididymis (mouse, macaque and human). Using the efferent ductule ligated (EDL) rat as a model to produce a sperm-free androgen-maintained epididymis, we have examined the factors regulating the expression of epididymal 2B1. RT-PCR and in situ transcript hybridization (ISH) studies showed that 2B1 mRNA is transcribed in the principal cells in all three regions of the epididymis. Its cognate protein was also detected by Western blot analysis in sperm-free cytosols from normal epididymis and found to undergo endoproteolytic cleavage into 2 subunits of similar size to the sperm-bound form. Immunohistochemistry with a monoclonal antibody to 2B1 confirmed that the protein is present in the epididymal epithelium and luminal secretions. The intensity of staining was much stronger in the sperm-free EDL epididymis than that in the normal (sperm-present) epididymis. The protein was shown to have hyaluronidase activity at neutral pH and both its quantity and activity appeared to be greater in the EDL epididymis. It is suggested that a soluble form of SPAM1 glycoprotein is synthesized and released in the epididymis and that in addition to androgens, its regulation may involve a cross-talk between the tubule epithelium and lumicrine factors, the latter possibly of testicular origin.

Animals↗
PubMed2004

Raptor protein contains a caspase-like domain.

Using state-of-the-art sequence analysis and structure-prediction methods a caspase-like domain in the N-terminal region of raptor proteins has been identified. This domain, which is characterized by the presence of invariant catalytic Cys-His dyad, is evolutionarily and structurally related to known caspases and might have protease activity. This finding suggests several unexpected aspects of raptor function in the target of rapamycin (TOR) signaling pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Recruitment of voluntary non-remunerated apheresis donors: the second five years' experience in Shenzhen.

The voluntary non-remunerated blood donation campaign in Shenzhen, China, was launched in 1993 and the smooth change from paid donors to unpaid took only a decade. In the first half the volunteer donation system and a sufficient blood supply was promoted and this paved the way for further development in the second half during which the non-remunerated donation system became substantial and integral due to recruitment for plateletapheresis and peripheral stem cells donation as well as whole blood donations. Ninety percent of the donors registered for plateletapheresis do donate and none of the twenty-three non-related donors with matched HLA genotypes broke their promise to donate their peripheral stem cells.

Altruism↗
PubMed2004

Members of a new group of chitinase-like genes are expressed preferentially in cotton cells with secondary walls.

Two homologous cotton (Gossypium hirsutum L.) genes, GhCTL1 and GhCTL2, encode members of a new group of chitinase-like proteins (called the GhCTL group) that includes other proteins from two cotton species, Arabidopsis, rice, and pea. Members of the GhCTL group are assigned to family GH19 glycoside hydrolases along with numerous authentic chitinases (http://afmb.cnrs-mrs.fr/CAZY/index.html), but the proteins have novel consensus sequences in two regions that are essential for chitinase activity and that were previously thought to be conserved. Maximum parsimony phylogenetic analyses, as well as Neighbor-Joining distance analyses, of numerous chitinases confirmed that the GhCTL group is distinct. A molecular model of GhCTL2 (based on the three-dimensional structure of a barley chitinase) had changes in the catalytic site that are likely to abolish catalytic activity while retaining potential to bind chitin oligosaccharides. RNA blot analysis showed that members of the GhCTL group had preferential expression during secondary wall deposition in cotton lint fiber. Cotton transformed with a fusion of the GhCTL2 promoter to the beta -d-glucuronidase gene showed preferential reporter gene activity in numerous cells during secondary wall deposition. Together with evidence from other researchers that mutants in an Arabidopsis gene within the GhCTL group are cellulose-deficient with phenotypes indicative of altered primary cell walls, these data suggest that members of the GhCTL group of chitinase-like proteins are essential for cellulose synthesis in primary and secondary cell walls. However, the mechanism by which they act is more likely to involve binding of chitin oligosaccharides than catalysis.

Amino Acid Sequence↗
PubMed2004

Effect of mitomycin C and vinblastine on FDG uptake of human nonsmall-cell lung cancer xenografts in nude mice.

This study was designed to preliminarily evaluate the use of positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG) for monitoring chemotherapy effects, using a nude-mouse model of human nonsmall-cell lung cancer (NSCLC), the Lu-99 cell line. Tumor-FDG uptakes and volumes were measured after administrating a single dose of mitomycin (MMC) and vinblastine (VLB) and then compared these for a nontherapy group. A significant reduction in tumor volume after either chemotherapy occurred and associated with significantly lower FDG uptake values than the control group (p < 0.001), as early as day 1. These observations suggest that FDG-PET may be useful for noninvasively monitoring the effects of cancer chemotherapy.

Animals↗
PubMed2004

Overexpression of the Arabidopsis 14-3-3 protein GF14 lambda in cotton leads to a "stay-green" phenotype and improves stress tolerance under moderate drought conditions.

The Arabidopsis gene GF14 lambda that encodes a 14-3-3 protein was introduced into cotton plants to explore the physiological roles that GF14 lambda might play in plants. The expression level of GF14 lambda under the control of the cauliflower mosaic virus 35S promoter varied in transgenic cotton plants, and lines that expressed GF14 lambda demonstrated a "stay-green" phenotype and improved water-stress tolerance. These lines wilted less and maintained higher photosynthesis than segregated non-transgenic control plants under water-deficit conditions. Stomatal conductance appears to be the major factor for the observed higher photosynthetic rates under water-deficit conditions. The stomatal aperture of transgenic plants might be regulated by GF14 lambda through some transporters such as H(+)-ATPase whose activities are controlled by their interaction with 14-3-3 proteins. However, since 14-3-3 proteins interact with numerous proteins in plant cells, many metabolic processes could be affected by the GF14 lambda overexpression. Whatever the mechanisms, the traits observed in the GF14 lambda-expressing cotton plants are beneficial to crops under certain water-deficit conditions.

14-3-3 Proteins↗
PubMed2004

Direct and repeat uses of tissue sections as templates for liquid-phase polymerase chain reaction amplification: applications and implications.

The liquid-phase polymerase chain reaction (PCR) technique is the most commonly used method for the amplification of genetic materials, although it requires the lysis of cells for DNA or RNA extraction, making it impossible to visualize the distribution and subcellular localization of the biomolecules. This study intended to assess whether tissue sections may be directly and repeatedly used as templates for liquid-phase PCR amplifications. Consecutive paraffin sections of breast tissues were placed on gamma-methacryloxypropyltrimethoxysilane-coated microscopic cover glasses perforated with a diamond knife into strips. After hematoxylin and eosin or immuno-staining, the strip of interest was inserted into a PCR tube for amplifications, and the adjacent strip with the same tissue was subject to microdissection, DNA extraction, and PCR amplifications. To use the strip repeatedly, it was transferred into a new PCR tube and amplified with a new primer set, after an initial amplification for 5 to 7 cycles. Then, initially amplified samples were amplified to a total of 40 cycles. An equal volume of PCR products from the strip and DNA extract were loaded side by side for electrophoresis and detection. The strip and DNA extract from the same tissue yielded a very comparable quality and quantity of PCR products with the same primer sets. The strip, however, could be repeatedly used for PCR amplifications with substantially more primer sets. In addition, the strip could be used for immunohistochemical or other molecular assays after PCR amplifications. Further studies with the same protocol on strips containing chromosomal spreads generated similar results.

DNA↗
PubMed2004

DBMap: a space-conscious data visualization and knowledge discovery framework for biomedical data warehouse.

Advances in digital imaging modalities as well as other diagnosis and therapeutic techniques have generated a massive amount of diverse data for clinical research. The purpose of this study is to investigate and implement a new intuitive and space-conscious visualization framework, called DBMap, to facilitate efficient multidimensional data visualization and knowledge discovery against the large-scale data warehouses of integrated image and nonimage data. The DBMap framework is built upon the TreeMap concept. TreeMap is a space constrained graphical representation of large hierarchical data sets, mapped to a matrix of rectangles, whose size and color represent interested database fields. It allows the display of a large amount of numerical and categorical information in limited real estate of the computer screen with an intuitive user interface. DBMap has been implemented and integrated into a large brain research data warehouse to support neurologic and neuroradiologic research at the University of California, San Francisco Medical Center. For imaging specialists and clinical researchers, this novel DBMap framework facilitates another way to better explore and classify the hidden knowledge embedded in medical image data warehouses.

Algorithms↗
PubMed2004

Symmetric fluoro-substituted diol-based HIV protease inhibitors. Ortho-fluorinated and meta-fluorinated P1/P1'-benzyloxy side groups significantly improve the antiviral activity and preserve binding efficacy.

HIV-1 protease is a pivotal enzyme in the later stages of the viral life cycle which is responsible for the processing and maturation of the virus particle into an infectious virion. As such, HIV-1 protease has become an important target for the treatment of AIDS, and efficient drugs have been developed. However, negative side effects and fast emerging resistance to the current drugs have necessitated the development of novel chemical entities in order to exploit different pharmacokinetic properties as well as new interaction patterns. We have used X-ray crystallography to decipher the structure-activity relationship of fluoro-substitution as a strategy to improve the antiviral activity and the protease inhibition of C2-symmetric diol-based inhibitors. In total we present six protease-inhibitor complexes at 1.8-2.3 A resolution, which have been structurally characterized with respect to their antiviral and inhibitory activities, in order to evaluate the effects of different fluoro-substitutions. These C2-symmetric inhibitors comprise mono- and difluoro-substituted benzyloxy side groups in P1/P1' and indanoleamine side groups in P2/P2'. The ortho- and meta-fluorinated P1/P1'-benzyloxy side groups proved to have the most cytopathogenic effects compared with the nonsubstituted analog and related C2-symmetric diol-based inhibitors. The different fluoro-substitutions are well accommodated in the protease S1/S1' subsites, as observed by an increase in favorable Van der Waals contacts and surface area buried by the inhibitors. These data will be used in the development of potent inhibitors with different pharmacokinetic profiles towards resistant protease mutants.

Amino Acids↗
PubMed2004

Vascular tone estimation in patients implanted with the AbioCor implantable replacement heart.

The AbioCor implantable replacement heart provides continuous hydraulic pressure data that are used for control purposes. The magnitude of the end systolic pressure spikes are compared to a preset threshold and used for controlling motor speeds to maintain a full stroke on every beat. Portions of the diastolic pressures of the left and the right side are averaged and can be used for left-right balance control. The mean right diastolic pressure may be used for beat rate (cardiac output) control. The systolic and diastolic hydraulic pressures of the left and right side are correlatable to the respective afterload and preload pressures. More importantly, with known hydraulic pump pressure-flow characteristics, cardiac output is derived. The slopes of the hydraulic pressure traces as a function of time are not used for control or monitoring purposes. However, the magnitudes and shapes of these slopes can provide information on the tones of a patient's vasculature. The ratio of the slope of the systolic pressure to that of the stroke volume yields the vascular tone given in mm Hg/cc. Due to pre-existing pulmonary complications, some AbioCor patients have pulmonary vascular tones that are substantially higher than their respective aortic tones by as much as a factor of four. Pulmonary tones as high as 2 mm Hg/cc, or approximately ten times the normal tone, are recorded. The ratio of averages of the aortic to the pulmonary tone range between 2.2 and 0.25 in patients implanted with the AbioCor compared with a normal value of 5 in subjects without pre-existing pulmonary diseases. The AbioCor implantable replacement heart's hydraulic drive system is capable of providing valuable physiological information, including estimates of physiological pressures, cardiac outputs, and vascular tones.

Aorta↗
PubMed2004

The trp RNA-binding attenuation protein of Bacillus subtilis regulates translation of the tryptophan transport gene trpP (yhaG) by blocking ribosome binding.

Expression of the Bacillus subtilis tryptophan biosynthetic genes (trpEDCFBA and pabA [trpG]) is regulated in response to tryptophan by TRAP, the trp RNA-binding attenuation protein. TRAP-mediated regulation of the tryptophan biosynthetic genes includes a transcription attenuation and two distinct translation control mechanisms. TRAP also regulates translation of trpP (yhaG), a single-gene operon that encodes a putative tryptophan transporter. Its translation initiation region contains triplet repeats typical of TRAP-regulated mRNAs. We found that regulation of trpP and pabA is unaltered in a rho mutant strain. Results from filter binding and gel mobility shift assays demonstrated that TRAP binds specifically to a segment of the trpP transcript that includes the untranslated leader and translation initiation region. While the affinities of TRAP for the trpP and pabA transcripts are similar, TRAP-mediated translation control of trpP is much more extensive than for pabA. RNA footprinting revealed that the trpP TRAP binding site consists of nine triplet repeats (five GAG, three UAG, and one AAG) that surround and overlap the trpP Shine-Dalgarno (S-D) sequence and translation start codon. Results from toeprint and RNA-directed cell-free translation experiments indicated that tryptophan-activated TRAP inhibits TrpP synthesis by preventing binding of a 30S ribosomal subunit. Taken together, our results establish that TRAP regulates translation of trpP by blocking ribosome binding. Thus, TRAP coordinately regulates tryptophan synthesis and transport by three distinct mechanisms: attenuation transcription of the trpEDCFBA operon, promoting formation of the trpE S-D blocking hairpin, and blocking ribosome binding to the pabA and trpP transcripts.

Amino Acid Transport Systems↗
PubMed2004

Identification of an antigenic determinant on the S2 domain of the severe acute respiratory syndrome coronavirus spike glycoprotein capable of inducing neutralizing antibodies.

Severe acute respiratory syndrome (SARS) is a life-threatening disease caused by a newly identified coronavirus (CoV), SARS-CoV. The spike (S) glycoprotein of CoV is the major structural protein responsible for induction of host immune response and virus neutralization by antibodies. Hence, knowledge of neutralization determinants on the S protein is helpful for designing protective vaccines. To analyze the antigenic structure of the SARS-CoV S2 domain, the carboxyl-terminal half of the S protein, we first used sera from convalescent SARS patients to test the antigenicity of 12 overlapping fragments spanning the entire S2 and identified two antigenic determinants (Leu 803 to Ala 828 and Pro 1061 to Ser 1093). To determine whether neutralizing antibodies can be elicited by these two determinants, we immunized animals and found that both of them could induce the S2-specific antisera. In some animals, however, only one determinant (Leu 803 to Ala 828) was able to induce the antisera with the binding ability to the native S protein and the neutralizing activity to the SARS-CoV pseudovirus. This determinant is highly conserved across different SARS-CoV isolates. Identification of a conserved antigenic determinant on the S2 domain of the SARS-CoV S protein, which has the potential for inducing neutralizing antibodies, has implications in the development of effective vaccines against SARS-CoV.

Amino Acid Sequence↗
PubMed2004

Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells.

Severe acute respiratory syndrome coronavirus (SARS-CoV) is the pathogen of SARS, which caused a global panic in 2003. We describe here the screening of Chinese herbal medicine-based, novel small molecules that bind avidly with the surface spike protein of SARS-CoV and thus can interfere with the entry of the virus to its host cells. We achieved this by using a two-step screening method consisting of frontal affinity chromatography-mass spectrometry coupled with a viral infection assay based on a human immunodeficiency virus (HIV)-luc/SARS pseudotyped virus. Two small molecules, tetra-O-galloyl-beta-D-glucose (TGG) and luteolin, were identified, whose anti-SARS-CoV activities were confirmed by using a wild-type SARS-CoV infection system. TGG exhibits prominent anti-SARS-CoV activity with a 50% effective concentration of 4.5 microM and a selective index of 240.0. The two-step screening method described here yielded several small molecules that can be used for developing new classes of anti-SARS-CoV drugs and is potentially useful for the high-throughput screening of drugs inhibiting the entry of HIV, hepatitis C virus, and other insidious viruses into their host cells.

Animals↗
PubMed2004

Ornithine decarboxylase is a target for chemoprevention of basal and squamous cell carcinomas in Ptch1+/- mice.

Solar ultraviolet B (UVB) radiation induces cutaneous ornithine decarboxylase (ODC), the first enzyme in the polyamine-biosynthesis pathway, which drives continued proliferation and clonal expansion of initiated (mutated) cells, leading to tumorigenesis. Therefore ODC is a potentially important target for chemoprevention of basal cell carcinomas (BCCs), the majority of which have mutations in the tumor-suppressor gene known as patched (PTCH). To assess this possibility, we first overexpressed ODC in the skin of Ptch1+/- mice using a keratin 6 (K6) promoter that directs constitutive ODC expression in the outer root sheath of the hair follicle. UVB irradiation of these mice accelerated induction of BCCs as compared with their Ptch1+/- littermates. To further verify the role of ODC in BCC tumorigenesis, we used an antizyme (AZ) approach to inhibit ODC activity in the Ptch1+/- mice. Ptch1+/- mice with AZ overexpression driven by the K6 promoter were resistant to the induction of BCCs by UVB. Furthermore, oral administration of the suicidal ODC inhibitor alpha-difluoromethylornithine reduced UVB-induced BCCs in Ptch1+/- mice. These results demonstrate the crucial importance of ODC for the induction of BCCs and indicate that chemopreventive strategies directed at inhibiting this enzyme may be useful in reducing BCCs in human populations.

Animals↗