Biomedical subjects

W Zhao

Publications and source records attributed to W Zhao.

At least 73 records · Page 4Linked to original sources

PubMed2001

Cloning and characterization of a human lysyl oxidase-like 3 gene (hLOXL3).

Using the PCR primers generated from human expressed sequence tag (EST), the cDNA of lysyl oxidase-like gene 3 (LOXL3), a new member of human lysyl oxidases gene family, was cloned from the human fetal brain mRNA. The predicted amino acid sequence of the hLOXL3 gene was highly homologous to mLOR2. Bioinformatics analysis shows that hLOXL3 protein is also a member of the scavenger receptor cysteine-rich family, which contains a 25 amino acids signal peptide. The hLOXL3 gene was mapped to human 2p13 locus by BLAST search and at least 14 exons were found. Expression of the hLOXL3 gene was detected in several human tissues and especially high in spleen and testis.

Amino Acid Oxidoreductases↗

PubMed2001

PDZ-binding kinase participates in spermatogenesis.

A cDNA clone denoted SPK (spermatogenesis-related protein kinase) was isolated from human fetal brain cDNA library. The deduced protein was 99% identical to human PDZ-binding kinase (PBK), which is a mitotic kinase. Its isoform, which is about 300 bp longer at 3' end, was also isolated in this study. SPK gene was assigned to human chromosome 8p21.2 by radiation hybrid. Northern blot analysis indicated that SPK mRNA was predominantly expressed in testis. SPK mRNA was localized to the outer cell layer of seminiferous tubules by in situ hybridization, suggesting involvement of it in the process of spermatogenesis.

Amino Acid Sequence↗

PubMed2001

Cloning and characterization of a novel human TEKTIN1 gene.

Tektins comprise a family of filament-forming proteins that are known to be coassembled with tubulins to form ciliary and flagellar microtubules. A new member of the tektin gene family was cloned from the human fetal brain cDNA library. We hence named it the human TEKTIN1 gene. TEKTIN1 cDNA consists of 1375 bp and has a putative open reading frame encoding 418 amino acids. The predicted protein is 48.3 kDa in size, and its amino acid sequence is 82% identical to that of the mouse, rat, and dog. One conserved peptide RPNVELCRD was observed at position number 323-331 of the amino acid sequence, which is a prominent feature of tektins and is likely to represent a functionally important protein domain. TEKTIN1 gene was mapped to the human chromosome 17 by BLAST search, and at least eight exons were found. Northern blot analysis indicated that TEKTIN1 was predominantly expressed in testis. By in-situ hybridization analysis, TEKTIN1 mRNA was localized to spermatocytes and round spermatids in the seminiferous tubules of the mouse testis, indicating that it may play a role in spermatogenesis.

Amino Acid Sequence↗

PubMed2001

Vibrational spectra study of the isomerizational reaction of nitryl hydride.

The vibrational spectral study of the isomerization reaction of nitryl hydride is presented in this paper. The isomerizational reaction includes old bond rupture, new bond formation and electronic transfer in the intramolecule. For the isomerizational reaction, the vibrational modes, the vibrational frequencies and the force constants of the reactant, the transition states and product are analyzed. The relationship and the change among them can confirm the rupture of bond, the formation of bond and the process of electron transfer.

Isomerism↗

PubMed2001

Three new sesquiterpene glycosides from Dendrobium nobile with immunomodulatory activity.

Dendroside A (1) and dendronobilosides A and B (2 and 3), three new sesquiterpene glycosides, have been isolated from the stems of Dendrobium nobile, a plant used in Chinese traditional medicine. Their structures and stereochemistry were determined as 10beta,12,14-trihydroxyalloaromadendrane 14-O-beta-D-glucopyranoside (1), 10,12-dihydroxypicrotoxane 10,12-di-O-beta-D-glucopyranoside (2), and 6alpha,10,12-trihydroxypicrotoxane 10-O-beta-D-glucopyranoside (3), respectively, on the basis of spectroscopic and chemical methods. Quantum chemistry calculations were used in support of the structural determination of 1. Compounds 1 and 2 were found to stimulate the proliferation of murine T and B lymphocytes in vitro, while compound 3 showed inhibitory activity in this same assay.

Adjuvants, Immunologic↗

PubMed2001

Identification of a human LNX protein containing multiple PDZ domains.

Recently PDZ domains have been recognized as crucial organizers of protein complexes at the plasma membrane. Here we report the cloning of a novel 3.7-kb cDNA LNX from a human fetal brain cDNA library. The deduced amino acid sequence shares about 88% identity with the p70 form of Lnx, which is the mouse ligand of Numb protein X. Motif analysis reveals five protein-interaction modules conservative to those in the Lnx protein, including four PDZ domains and a NPXY motif for binding of the Numb PTB domain. Northern blot analysis shows that the length of the transcript in brain is distinct from those in other tissues. By radiation hybrid mapping, we localize the LNX gene to human chromosome 4q12 between marker D4S1577 and marker D4S1594. We predict that LNX may be important for the organization of signaling complexes in Numb-involved pathways or pathways regulated by other PTB-containing proteins.

Amino Acid Motifs↗

PubMed2001

Molecular cloning and characterization of a novel Dehydrogenase/reductase (SDR family) member 1 genea from human fetal brain.

Short-chain dehydrogenases/reductases (SDR) constitute a large protein family of NAD(P)(H)-dependent oxidoreductase. They are defined by distinct, common sequence motifs and show a wide range of substrate specialisms. By large-scale sequencing analysis of a human fetal brain cDNA library, we isolated a novel human SDR-type dehydrogenase/reductase gene named Dehydrogenase/reductase (SDR family) member 1 (DHRS1). The DHRS1 cDNA is 1411 base pair in length, encoding a 314-amino-acid polypeptide which has a SDR motif. Northern blot reveals two bands, of about 0.9 and 1.4 kb in size. These two forms are expressed in many tissues. The DHRS1 gene is localized on chromosome 14q21.3. It has 9 exons and spans 9.2 kb of the genomic DNA.

Amino Acid Sequence↗

PubMed2001

A novel human hydroxysteroid dehydrogenase like 1 gene (HSDL1) is highly expressed in reproductive tissues.

We report the cloning and characterization of a novel human hydroxysteroid dehydrogenase like gene (HSDL1) located on human chromosome 16q24.2. The HSDL1 cDNA is 3407 base pair in length, encoding a 309 amino acid polypeptide related to human 17beta-HSD3. Northern blot reveals that the HSDL1 is highly expressed in testis and ovary. In situ hybridization indicates that the expression of HSDL1 is predominantly increased in the prostate cancer tissue compared with the normal prostate tissue, which suggests that the gene expression is important to the arising of prostate cancer.

Amino Acid Sequence↗

PubMed2001

Gene expression profiles during long-term memory consolidation.

Changes in gene expression have been postulated to occur during long-term memory (LTM). We used high-density cDNA microarrays to assess changes in gene expression 24 h after rabbit eye blink conditioning. Paired animals were presented with a 400 ms, 1000 Hz, 82 dB tone conditioned stimulus that coterminated with a 100 ms, 60 Hz, 2 mA electrical pulse unconditioned stimulus. Unpaired animals received the same conditioned and unconditioned stimuli but presented in an explicitly unpaired manner. Differences in expression levels between paired and unpaired animals in the hippocampus and cerebellar lobule HVI, two regions activated during eye blink conditioning, indicated the involvement of novel genes as well as the participation of previously implicated genes. Patterns of gene expression were validated by in situ hybridization. Surprisingly, the data suggest that an underlying mechanism of LTM involves widespread decreased, rather than increased, gene expression. These results demonstrate the feasibility and utility of a cDNA microarray system as a tool for dissecting the molecular mechanisms of associative memory.

Animals↗

PubMed2001

Talampanel, a novel noncompetitive AMPA antagonist, is neuroprotective after traumatic brain injury in rats.

Talampanel [(R)-7-acetyl-5-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxolo[4,5-h][2,3] benzodiazepine] is an orally active noncompetitive antagonist of the AMPA subtype of glutamate excitatory amino acid receptors. The purpose of this study was to determine whether treatment with talampanel would protect in a rat model of traumatic brain injury (TBI). Twenty-four hours prior to TBI, a fluid-percussion interface was positioned parasagittally over the right cerebral cortex. On the following day, fasted rats were anesthetized with 3% halothane, 70% nitrous oxide, and a balance of oxygen; mechanically ventilated and physiologically regulated; and subjected to right parieto-occipital parasagittal fluid-percussion injury (1.5-2.0 atm). The agent (talampanel, bolus infusion of 4 mg/kg followed by infusion of 4 mg/kg/h over 72 h) or vehicle was administered i.v. starting at either 30 min or 3 h after trauma. Seven days after TBI, brains were perfusion-fixed, coronal sections at various levels were digitized, and contusion areas were measured. Treatment with talampanel, when instituted 30 min after trauma, significantly reduced total contusion area compared to vehicle-treated rats (0.54 +/- 0.25 vs. 1.79 +/- 0.42 mm2, respectively). When talampanel treatment was begun at 3 h, the neuroprotective effect of the drug was lost. In addition, treatment with talampanel starting at 30 min significantly attenuated neuronal damage in all three subsectors of the hippocampal CA1 sector compared to vehicle-treated rats (normal-neuron counts, right (ipsilateral) medial CA1: 80.3 +/- 2.0 [talampanel] vs. 66.3 +/- 2.1 [vehicle] (mean +/- SEM); middle CA1: 71.5 +/- 2.0 vs. 60.3 +/- 2.2; lateral CA1: 74.5 +/- 3.0 vs. 63.0 +/- 3.2, respectively). By contrast, when talampanel treatment was begun at 3 h, normal pyramidal-neuron counts were almost identical in both groups. Our findings document that talampanel therapy instituted 30 min after trauma significantly reduces histological damage.

Animals↗

PubMed2001

Quantitative analysis of microvascular alterations in traumatic brain injury by endothelial barrier antigen immunohistochemistry.

Endothelial barrier antigen (EBA) is a protein triplet located in the plasma membrane of microvascular endothelium and selectively expressed in the normal nervous system. In this study, microvascular alterations following traumatic brain injury were studied using EBA immunohistochemistry. Anesthetized, physiologically regulated, normothermic Sprague-Dawley rats received moderate (1.5-2.0 atm) parieto-occipital parasagittal fluid-percussion traumatic brain injury (TBI). Control rats were subjected to similar anesthesia and physiological monitoring. Seven days after operative procedures, brains were perfusion-fixed, and coronal sections were reacted for EBA immunohistochemistry using a monoclonal antibody to rat EBA. Selected sections were reacted for isolectin B4 histochemistry. Computerized image analysis was used to compute numbers of EBA-immunopositive vascular profiles and mean vascular profile areas. In control brains, virtually all brain microvessels were clearly and positively immunostained, and antibody binding was specific for blood vessels. In rats with TBI, EBA immunoreactivity was greatly reduced in the zone of cortical contusion. Within the core contusion, fractional areas occupied by vascular profiles were markedly reduced (on average, by 57%), vascular profile counts were diminished, and lectin histochemistry revealed a robust inflammatory response with abundant macrophages. Taken together, these findings were thought to indicate frank microvascular destruction. At adjacent peri-contusional sites, the intensity of EBA immunostaining was also diminished; and vascular profile counts were reduced at adjacent cortical sites and homologous contralateral sites. The latter findings were interpreted as sublethal microvascular alterations possibly related to cerebral edema. The present results confirm that EBA is a specific immunohistochemical marker of normal central nervous system microvessels; that it is suitable for use in formaldehyde-fixed material; and that it is useful in quantitatively assessing microvascular alterations observed at contusional, peri-contusional and more remote sites following traumatic brain injury.

Animals↗

PubMed2001

Candidate foods in the Asia-Pacific region for cardiovascular protection: Oriental tea.

Chinese tea and the major health effects include: antimicrobial, anti-ultraviolet radiation, anticancer, lowering blood lipid and glucose, and protecting against coronary heart diseases. In contrast to the extensive studies on the protective effects of tea on cancer, fewer studies on the health effects of tea on cardiovascular diseases (CVD) have been published. This paper summarises the research results on the possible protective effects of tea on CVD available in China. The results from animal studies clearly demonstrated that tea pigments are effective in lowering blood lipid levels and preventing plaque formation in the aorta. However, the evidence of tea pigments in protecting ischemia heart disease (IHD) in humans is less convincing. One large well-designed ecological study reported an inverse correlation between tea drinking and IHD mortality; but the inverse correlation disappeared after controlling possible confounding factors. However, the effects in improving blood lipid levels and rheology biomarkers in hyperlipidemia subjects or CVD patients by tea pigments seem promising. However, these studies were not well-designed, controlled randomized clinical trials. This made the assessment difficult and inconclusive.

Animals↗

PubMed2001

Implications from and for food cultures for cardiovascular disease: diet, nutrition and cardiovascular diseases in China.

The change of lifestyle of Chinese people, along with the development of the national economy, has caused significant changes of the disease pattern in China. This includes the shift from predominantly communicable diseases to non-communicable diseases, such as cancer, cardiovascular disease, diabetes and obesity. This paper summarises epidemiology research results on the relationship between diet, nutrition and cardiovascular diseases (CVD) available in China. Most data used in this paper are from correlation studies. While the information is very useful in generating hypotheses on dietary and nutritional risk factors for CVD, both prospective studies and population-based intervention trials are needed to further verify these hypotheses. The information in this review clearly shows that diet and nutrition play important roles in the occurrence of CVD and hypertension in the Chinese population. Therefore, dietary means should be an important part of the strategies for the control of CVD and hypertension in China.

Cardiovascular Diseases↗

PubMed2001

Effects of characteristic x rays on the noise power spectra and detective quantum efficiency of photoconductive x-ray detectors.

The effects of K fluorescence on the imaging performance of photoconductor-based x-ray imaging systems are investigated. A cascaded linear systems model was developed, where a parallel cascaded process was implemented to take into account the effect of K-fluorescence reabsorption on the modulation transfer function (MTF), noise power spectrum (NPS), and the spatial frequency dependent detective quantum efficiency [DQE(f)] of an imaging system. The investigation was focused on amorphous selenium (a-Se), which is the most highly developed photoconductor material for x-ray imaging. The results were compared to those obtained with Monte Carlo simulation using the same imaging condition and detector parameters, so that the validity of the cascaded linear system model could be confirmed. Our results revealed that K-fluorescence reabsorption in a-Se is responsible for a 18% drop in NPS at high spatial frequencies with an incident x-ray photon energy of E=20 keV (which is just above the K edge of 12.5 keV). When E increases to 60 keV, the effects of K-fluorescence reabsorption on NPS decrease to approximately 12% at high spatial frequencies. Because the high frequency drop is present in both MTF and NPS, the effect of K fluorescence on DQE(f) is minimal, especially for E that is much higher than the K edge. We also applied the cascaded linear system model to a newly developed compound photoconductor, lead iodide (PbI2), and found that at 60 keV there is a high frequency drop in NPS of 19%. The calculated NPS were compared to previously published measurements of PbI2 detectors.

Diagnostic Imaging↗

PubMed2001

Malnutrition alters the innate immune response and increases early visceralization following Leishmania donovani infection.

Malnutrition is a risk factor for the development of visceral leishmaniasis. However, the immunological basis for this susceptibility is unknown. We have developed a mouse model to study the effect of malnutrition on innate immunity and early visceralization following Leishmania donovani infection. Three deficient diets were studied, including 6, 3, or 1% protein; these diets were also deficient in iron, zinc, and calories. The control diet contained 17% protein, was zinc and iron sufficient, and was provided ab libitum. Three days after infection with L. donovani promastigotes, the total extradermal (lymph nodes, liver, and spleen) and skin parasite burdens were equivalent in the malnourished (3% protein) and control mice, but in the malnourished group, a greater percentage (39.8 and 4.0%, respectively; P = 0.009) of the extradermal parasite burden was contained in the spleen and liver. The comparable levels of parasites in the footpads in the two diet groups and the higher lymph node parasite burdens in the well-nourished mice indicated that the higher visceral parasite burdens in the malnourished mice were not due to a deficit in local parasite killing but to a failure of lymph node barrier function. Lymph node cells from the malnourished, infected mice produced increased levels of prostaglandin E(2) (PGE(2)) and decreased levels of interleukin-10. Inducible nitric oxide synthase activity was significantly lower in the spleen and liver of the malnourished mice. Thus, malnutrition causes a failure of lymph node barrier function after L. donovani infection, which may be related to excessive production of PGE(2) and decreased levels of IL-10 and nitric oxide.

Animals↗

PubMed2001

Leishmania donovani p36(LACK) DNA vaccine is highly immunogenic but not protective against experimental visceral leishmaniasis.

The acquisition of immunity following subclinical or resolved infection with the intracellular parasite Leishmania donovani suggests that vaccination could prevent visceral leishmaniasis (VL). The LACK (Leishmania homolog of receptors for activated C kinase) antigen is of interest as a vaccine candidate for the leishmaniases because of its immunopathogenic role in murine L. major infection. Immunization of mice with a truncated (24-kDa) version of the 36-kDa LACK antigen, delivered in either protein or DNA form, was found previously to protect against cutaneous L. major infection by redirecting the early T-cell response away from a pathogenic interleukin-4 (IL-4) response and toward a protective Th1 response. The amino acid sequence of the Leishmania p36(LACK) antigen is highly conserved, but the efficacy of this vaccine antigen in preventing disease caused by strains other than L. major has not been determined. We investigated the efficacy of a p36(LACK) DNA vaccine against VL because of the serious nature of this form of leishmaniasis and because it was unclear whether the LACK vaccine would be effective in a model where there was not a dominant pathogenic IL-4 response. We demonstrate here that although the LACK DNA vaccine induced a robust parasite-specific Th1 immune response (IFN-gamma but not IL-4 production) and primed for an in vivo T-cell response to inoculated parasites, it did not induce protection against cutaneous or systemic L. donovani challenge. Coadministration of IL-12 DNA with the vaccine did not enhance the strong vaccine-induced Th1 response or augment a protective effect.

Animals↗

PubMed2001

Central modulation of the NO/cGMP pathway affects the MPOA-induced intracavernous pressure response.

Alterations in the nitric oxide (NO)/cGMP levels in hypothalamic nuclei, including the medial preoptic area (MPOA), regulate critical aspects of sexual behavior and penile reflexes. However, the effects of altered central nervous system (CNS) NO/cGMP levels at the end organ level, that is, on the magnitude/quality of the erection so achieved [intracavernous pressure (ICP) response], has yet to be evaluated. The goal of this report was to evaluate the effects of intrathecal administration of modulators of NO and cGMP levels on ICP responses to stimulation of the MPOA and cavernous nerve in rats in vivo. In all cases, intrathecal administration of compounds that increase and decrease cGMP and NO levels, respectively, was associated with corresponding increases and decreases in the MPOA-stimulated ICP response. Specifically, sodium nitroprusside (SNP), 8-bromo-cGMP, and sildenafil increased the MPOA-stimulated ICP response, whereas N(omega)-nitro-L-arginine methyl ester reduced it. None of the intrathecal treatments had detectable effects on blood pressure or the cavernous nerve-stimulated ICP response, although intravenous sildenafil increased the latter. These data clearly indicate that intrathecal drug administration affects central and not peripheral neural mechanisms and, moreover, documents that CNS NO/cGMP levels can affect erectile capacity per se (i.e., ICP) in the rat model.

Animals↗

PubMed2001

Bladder injection of "naked" hSlo/pcDNA3 ameliorates detrusor hyperactivity in obstructed rats in vivo.

The goal of these studies was to examine the potential utility of bladder instilled K+ channel gene therapy with hSlo cDNA (i.e., the maxi-K channel) to ameliorate bladder overactivity in a rat model of partial urinary outlet obstruction. Twenty-two female Sprague-Dawley rats were subjected to partial urethral (i.e., outlet) obstruction, with 17 sham-operated control rats run in parallel. After 6 wk of obstruction, suprapubic catheters were surgically placed in the dome of the bladder in all rats. Twelve obstructed rats received bladder instillation of 100 microg of hSlo/pcDNA in 1 ml PBS during catheterization, and another 10 obstructed rats received 1 ml PBS (7 rats) or 1 ml PBS containing pcDNA only (3 rats). Two days after surgery cystometry was performed on all animals to examine the characteristics of the micturition reflex in conscious and unrestrained rats. Obstruction was associated with a three- to fourfold increase in bladder weight and alterations in virtually every micturition parameter estimate. PBS-injected obstructed rats routinely displayed spontaneous bladder contractions between micturitions. In contrast, hSlo injection eliminated the obstruction-associated bladder hyperactivity, without detectably affecting any other cystometric parameter. Presumably, expression of hSlo in rat bladder functionally antagonizes the increased contractility normally observed in obstructed animals and thereby ameliorates bladder overactivity. These initial observations indicate a potential utility of gene therapy for urinary incontinence.

Administration, Intravesical↗