Biomedical subjects

Hong Liu

Publications and source records attributed to Hong Liu.

392 records · Page 22Linked to original sources

PubMed2002

Inhibiting effects of low-molecular weight heparin and adrenocortical hormone on hemolysis of red cells in patients with paroxysmal nocturnal hemoglobinuria in vitro.

OBJECTIVE: To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. METHODS: Using Ham's test and micro-complement lysis sensitive test (mCLST), the changes in hemolysis of red cells from 6 typical PNH cases were examined after adding LMWH and dexamethasone in different concentrations into the test solution in vitro. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied using the activated partial thromboplastin time (APTT) test. RESULTS: Both LMWH and dexamethasone inhibited the hemolysis of PNH red cells, and they also showed a synergistic effect. The inhibiting effects were dose-dependent. Moreover, a tolerable dose of LMWH induced a limited prolongation of APTT. Dexamethasone showed two possible mechanisms in the inhibition of PNH red cells hemolysis through Ham's test and mCLST, respectively: (1) inhibiting both antibodies binding to red cells and (2) the initiation of the activation of complement 3 (C3). LMWH could inhibit hemolysis as determined by both Ham's test and mCLST, which indicated that LMWH could block the activation of complement cascade. CONCLUSIONS: Both LMWH and dexamethasone could inhibit hemolysis in PNH, and they showed a synergistic effect. Their mechanisms of inhibiting hemolysis differed from each other. Furthermore, a tolerable dose of LMWH induced a limited prolongation of APTT. LMWH might be useful for controlling acute hemolysis in patients with PNH and reducing the dose of adrenocortical hormone.

Dexamethasone↗

PubMed2002

Analysis of Female Breast Cancer Descriptive Epidemiology in Tianjin, China.

To take effective measures for prevention and achieve the goal of reducing the incidence and mortality rate from breast cancer, the method of descriptive epidemiology was used to study the situation regarding female breast cancer in Tianjin. There is an increasing trend for the incidence rate (increasing 51% during the period from 1981 to 1997), though the absolute value is still low in comparison with the developed countries in the world. Furthermore, the mortality rate of breast cancer has been decreasing constantly (decreasing 38% during the same period), while the 5-year, 10-year and 15-year survival rate increased. This may be mostly attributable to work leading to early detection and early diagnosis of breast cancer.

Journal Article↗

PubMed2001

Structure-function relationships of the raloxifene-estrogen receptor-alpha complex for regulating transforming growth factor-alpha expression in breast cancer cells.

Amino acid Asp-351 in the ligand binding domain of estrogen receptor alpha (ERalpha) plays an important role in regulating the estrogen-like activity of selective estrogen receptor modulator-ERalpha complexes. 4-Hydroxytamoxifen is a full agonist at a transforming growth factor alpha target gene in situ in MDA-MB-231 human breast cancer cells stably transfected with the wild-type ERalpha. In contrast, raloxifene (Ral), which is also a selective estrogen receptor modulator, is a complete antiestrogen in this system. Because D351G ERalpha allosterically silences activation function-1 activity in the 4-hydroxytamoxifen-ERalpha complex with the complete loss of estrogen-like activity, we examined the converse interaction of amino acid 351 and the piperidine ring of the antiestrogen side chain of raloxifene to enhance estrogen-like action. MDA-MB-231 cells were either transiently or stably transfected with Asp-351 (the wild type), D351E, D351Y, or D351F ERalpha expression vectors. Profound differences in the agonist and antagonist actions of Ralcenter dotERalpha complexes were noted only in stable transfectants. The agonist activity of the Ralcenter dotERalpha complex was enhanced with D351E and D351Y ERalpha, but raloxifene lost its agonist activity with D351F ERalpha. The distance between the piperidine nitrogen of raloxifene and the negative charge of amino acid 351 was critical for estrogen-like actions. The role of the piperidine ring in neutralizing Asp-351 was addressed using compound R1h, a raloxifene derivative replacing the nitrogen on its piperidine ring with a carbon to form cyclohexane. The derivative was a potent agonist with wild type ERalpha. These results support the concept that the side chain of raloxifene shields and neutralizes the Asp-351 to produce an antiestrogenic ERalpha complex. Alteration of either the side chain or its relationship with the negative charge at amino acid 351 controls the estrogen-like action at activating function 2b of the selective estrogen receptor modulator ERalpha complex.

Breast Neoplasms↗

PubMed2001

Coordinate effects of human immunodeficiency virus type 1 protein Tat and cellular protein Puralpha on DNA replication initiated at the JC virus origin.

JC virus (JCV) causes progressive multifocal leukoencephalopathy, a demyelinating disease in brains of individuals with AIDS. Previous work has shown that the Tat protein, encoded by human immunodeficiency virus type 1 (HIV-1), can interact with cellular protein Puralpha to enhance both TAR-dependent HIV-1 transcription and JCV late gene transcription. Tat has been shown to activate JCV transcription through interaction with Puralpha, which binds to promoter sequence elements near the JCV origin of replication. DNA footprinting has shown that Puralpha and large T-antigen cooperatively interact at several binding sites in the origin and transcriptional control region. Overexpression of Puralpha inhibits replication initiated at the JCV origin by T-antigen. In transfected glial cells Tat reversed this inhibition and enhanced DNA replication. In an in vitro replication system maximal activation by Tat, more than sixfold the levels achieved with T-antigen alone, was achieved in the presence of Puralpha. Effects of mutant Tat proteins on both activation of replication and binding to Puralpha have revealed that Cys22 exerts a conformational effect that affects both activities. The origin of an archetypal strain of JCV was less susceptible to activation of replication by Tat relative to the rearranged Mad-1 strain. These results have revealed a previously undocumented role for Tat in DNA replication and have indicated a regulatory role for JCV origin auxiliary sequences in replication and activation by Tat.

Antigens, Viral, Tumor↗

PubMed2000

Fenfluramine challenge in anxious children.

The study objective was to determine if serotonergic challenge with oral racemic fenfluramine would differentiate between childhood anxiety disorders in comparison to normal controls. Subjects were 24 children with anxiety diagnoses (DSM-IIIR) by structured interview, and 14 normal controls (ages 7 - 14 years) matched for age and sex. All subjects were given a standard challenge dose of d,1-fenfluramine (1 mg/kg) followed by serial assessments of cardiovascular, neurohormonal, and mood parameters over a five hour period. In response to fenfluramine, controls demonstrated increases in subjective anxiety and systolic blood pressure relative to anxious subjects. Fenfluramine was safely tolerated and did not induce panic symptoms in any subject. Exaggerated prolactin response to fenfluramine differentiated an obsessive - compulsive disorder (OCD) subset from both controls and other anxiety disorders. Fenfluramine challenge differentiates anxious children from healthy controls by elevated anxiety ratings and systolic blood pressure in controls. Increased prolactin response to fenfluramine discriminates children with obsessive - compulsive disorder from both healthy children and children with other anxiety diagnoses. As adults with OCD appear to demonstrate a blunted prolactin response to fenfluramine challenge, the serotonin pathways involved may differ between 'early' and 'late' onset disorder, or the serotonin substrates tapped by this challenge may change over time. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗

PubMed2000

Construction and Characterization of Recombinant Adenoviruses Expressing Biologically Active Human Brain-derived Neurotrophic Factor and Neurotrophin-3.

In order to deliver brain-derived neurotrophic factor(BDNF) and neurotrophin-3(NT3) into CNS to prevent or reduce degeneration of CNS neurons in human neurodegenerative diseases and neuron injuries, recombinant adenoviruses Ad-BDNF and Ad-NT3 were constructed. BDNF and NT3 genes were inserted into an E1-substituted adenovirus shuttle plasmid, respectively, and were driven by the human cytomegalovirus immediate-early gene promoter/enhancer. After cotransfection into 293 cells with the adenovirus plasmid pJM17, the recombinant adenovirus Ad-BDNF and Ad-NT3 were propagated in 293 cells via homologous recombination. After two rounds of CsCl centrifugation, the human recombinant adenovirus Ad-BDNF and Ad-NT3 were obtained with titer of 1x10(12) and 8x10(11) pfu/ml, respectively. To examine the expression of BDNF and NT3, HeLa cells were infected with Ad-BDNF and Ad-NT3, respectively. RT-PCR, Western blot and ELISA analysis results showed that BDNF and NT3 genes could be transcribed and translated in Ad-BDNF and Ad-NT3 infected HeLa cells. And the culture media containing 10% conditioned medium of Ad-BDNF and Ad-NT3 infected Hela cells could induce the neurite outgrowth from E8 dorsal root ganglion neurons.

Journal Article↗

PubMedDate not supplied

Focused combinatorial library design based on structural diversity, druglikeness and binding affinity score.

The advent of focused library and virtual screening has reduced the disadvantage of combinatorial chemistry and changed it to a realizable and cost-effective tool in drug discovery. Usually, genetic algorithms (GAs) are used to quickly finding high-scoring molecules by sampling a small subset of the total combinatorial space. Therefore, scoring functions play essential roles in focused library design. Reported here is our initial attempt to establish a new approach for generating a target-focused library using the combination of the scores of structural diversity and binding affinity with our newly improved drug-likeness scoring functions. Meanwhile, a software package, named LD1.0, was developed on the basis of the new approach. One test on a cyclooxygenase (COX)2-focused library successfully reproduced the structures that have been experimentally studied as COX2-selective inhibitors. Another test is on a peroxisome proliferator-activated receptors gamma-focused library design, which not only reproduces the key fragments in the approved (thiazolidinedione) TZD drugs, but also generates some new structures that are more active than the approved drugs or published ligands. Both of the two tests took approximately 15% of the running time of the ordinary molecular docking method. Thus, our new approach is an effective, reliable, and practical way for building up a properly sized focused library with a high hit rate, novel structure, and good ADME/T profile.

Algorithms↗

PubMedDate not supplied

Strategy for discovering chemical inhibitors of human cyclophilin a: focused library design, virtual screening, chemical synthesis and bioassay.

The discovery of cyclophilin A (CypA) inhibitor is now of special interest in the treatment of immunological disorders. In this work, using a strategy integrating focused combinatorial library design, virtual screening, chemical synthesis, and bioassay, a series of novel small molecular CypA inhibitors have been discovered. First, using the fragments taken from our previously discovered CypA inhibitors (Bioorg. Med. Chem. 2006, 14, 2209-2224) as building blocks, we designed a focused combinatorial library containing 255 molecules employing the LD1.0 program (J. Comb. Chem. 2005, 7, 398-406) developed by us. Sixteen compounds (1a-e, 2a-b, 3a-b, and 4a-g) were selected by using virtual screening against the X-ray crystal structure of CypA as well as druglike analysis for further synthesis and bioassay. All these sixteen molecules are CypA binders with binding affinities (K(D) values) ranging from 0.076 to 41.0 microM, and five of them (4a, 4c, and 4e-g) are potent CypA inhibitors with PPIase inhibitory activities (IC(50) values) of 0.25-6.43 microM. The hit rates for binders and inhibitors are as high as 100% and 31.25%, respectively. Remarkably, both the binding affinity and inhibitory activity of the most potent compound increase approximately 10 times than that of the most active compound discovered previously. The high hit rate and the high potency of the new CypA inhibitors demonstrated the efficiency of the strategy for focused library design and screening. In addition, the novel chemical entities reported in this study could be leads for discovering new therapies against the CypA pathway.

Binding Sites↗

PubMedDate not supplied

Characteristics of a charged-coupled-device-based optical mapping system for the study of cardiac arrhythmias.

We develop an optical fluorescent mapping system that is able to record the action potential wavefront propagation within cardiac tissue samples with high spatial and temporal resolutions. The system's main component, the fluorescence acquisition device (customized CCD camera), offers a high spatial resolution of 128 x 128 pixels, with 12-bit digitization and a frame rate of 490 frames/s. The system is designed and implemented to image an area of approximately 20 x 20 mm at its minimum object distance of 140 mm, corresponding to a spatial resolution of approximately 3 line pairs/mm. Experiments using this system with di-4-ANEPPS-stained canine cardiac tissues with stimulated action potentials through external electrodes result in successful mappings of the distribution and propagation of the action potential wavefronts, showing the system's sensitivity to the change in fluorescence intensity in regions of action potentials. These data demonstrate this optical mapping system as a powerful device in the study of cardiac arrhythmia mechanisms.

Action Potentials↗

PubMedDate not supplied

Enhancement of laser cancer treatment by a chitosan-derived immunoadjuvant.

A chitosan derivative, glycated chitosan (GC), has been used as an immunostimulant for cancer treatment in laser immunotherapy. The function of GC is to enhance the host immune response after direct cancer cell destruction by a selective laser photothermal interaction. To further test its effects, laser immunotherapy was extended to include several different adjuvants for immunological stimulation and to include photodynamic therapy (PDT) as a different tumor-destruction mechanism. Complete Freund (CF) adjuvant, incomplete Freund (IF) adjuvant and Corynebacterium parvum (CP) were selected for treatment of metastatic mammary tumors in rats, in combination with a selective photothermal interaction. The solution of the immunoadjuvants admixed with indocyanine green (ICG), a light-absorbing dye, was injected directly into the tumors, followed by noninvasive irradiation of an 805 nm laser. Combined with PDT, in the treatment of tumors in mice, GC was administered peritumorally immediately after laser irradiation. The survivals of treated animals were compared with untreated control animals. In the treatment of rat tumors, CF, IF and CP raised the cure rates from 0% to 18%, 7% and 9%, respectively. In comparison, GC resulted in a 29% long-term survival. In the treatment of EMT6 mammary sarcoma in mice, GC of 0.5% and 1.5% concentrations increased the cure rates of Photofrin-based PDT treatment from 38% to 63% and 75%, respectively. In the treatment of Line 1 lung adenocarcinoma in mice, a 1.67% GC solution enabled a noncurative meso-substituted tetra(meta-hydroxy-phenyl)chlorin-based PDT to cure 37% of the tumor-bearing mice. The experimental results of this study confirmed our previous studies, showing that immunoadjuvants played an active role in laser-related cancer treatment and that GC significantly enhanced the efficacy of laser cancer treatment.

Adjuvants, Immunologic↗

PubMedDate not supplied

Capillary electrophoresis separation of autocondensation glycation products of glucosamine.

Glucosamine nonenzymatically forms autocondensation glycation products under physiological conditions. Many studies have reported the effectiveness of oral doses of glucosamine alone or in combination with the galactosamine containing chondroitin in treating osteoarthritis. However, none of these studies has considered whether it is the glucosamine itself and/or one or more of its autocondensation products that exert this effect. A capillary electrophoresis method was developed to monitor the nonenzymatic formation of autocondensation glycation products of glucosamine, galactosamine, and mannosamine under physiological conditions. Major components were detected and separated by CE with a UV detector. The effects of concentration and incubation time on product species were determined. The method described is simple, rapid, and effective.

Electrophoresis, Capillary↗

PubMedDate not supplied

Characteristics of nerve root compression caused by degenerative lumbar spinal stenosis with scoliosis.

BACKGROUND CONTEXT: In degenerative lumbar spinal stenosis with scoliosis (DLS), many authors stated that nerve root compression is almost always seen on the concave side of the scoliosis, and L4 and L5 nerve roots are the most often involved. However, there are few reports on the relationship between nerve root compression and the pattern of scoliosis. PURPOSE: To investigate the factors that may contribute to radiculopathy in DLS and their association with the pattern of the scoliosis. STUDY DESIGN: Retrospective analysis. METHODS: Twenty-two consecutive patients with DLS with radiculopathy were examined. The symptomatic nerve roots were determined by pain distribution, neurological findings and nerve root infiltration using lidocaine. The compressive factors were diagnosed by magnetic resonance imaging or myelography, discography, computed tomography after myelography or discography and radiculography. The pattern of scoliosis was determined in plain radiographs. We evaluated the correlation between the affected nerve root and the compressive factors or the pattern of the scoliosis. RESULTS: The L3 root was affected in 23% of patients; L4 root in 68%, L5 root in 55% and S1 root in 18%. L3 and L4 roots were more compressed by foraminal or extraforaminal stenosis on the concave side of the curve, whereas L5 and S1 roots were commonly affected by lateral recess stenosis on the convex side. The Cobb angle and the lateral slip of the cases in which L3 or L4 root was affected were significantly larger than in cases in which L5 or S1 root was compressed. CONCLUSIONS: In the treatment of radiculopathy caused by DLS, it is important to bear in mind that L3 or L4 roots were more strongly compressed by foraminal or extraforaminal stenosis at the concave side of the curve, whereas L5 or S1 nerve roots were affected more by lateral recess stenosis at the convex side of the curve.

Aged↗

PubMedDate not supplied

Diffusion-weighted and fluid-attenuated inversion recovery imaging in Creutzfeldt-Jakob disease: high sensitivity and specificity for diagnosis.

BACKGROUND AND PURPOSE: Abnormalities on diffusion-weighted images (DWIs) and fluid-attenuated inversion recovery (FLAIR) images are reported in Creutzfeldt-Jakob disease (CJD). To our knowledge, no large study has been conducted to determine the sensitivity and specificity of DWI and FLAIR imaging for diagnosing CJD. METHODS: Two neuroradiologists, blinded to diagnosis, retrospectively evaluated DWI and FLAIR images from 40 patients with probable or definite CJD and 53 control subjects with other forms of dementia and rated the likelihood of CJD on the basis of the imaging findings. RESULTS: DWI and FLAIR imaging was 91% sensitive, 95% specific, and 94% accurate for CJD. Interrater reliability was high (kappa = 0.93). Sensitivity was higher for DWI than FLAIR imaging. Abnormalities involved cortex and deep gray matter (striatum and/or thalamus) in 68% of patients with CJD, cortex alone in 24%, and deep gray matter alone in 5%. The most typical and specific patterns were corresponding hyperintensity on both FLAIR images and DWIs confined to the gray matter in the cortex, striatum, medial and/or posterior thalamus, or a combination of these areas. Narrow-window soft-copy review of artifact-free DWIs and FLAIR images and recognition of the normal variation in cortical signal intensity proved critical for successful differentiation of CJD from other dementias. CONCLUSION: Because specific patterns of abnormality on DWI and FLAIR images are highly sensitive and specific for CJD, these sequences should be performed whenever CJD is suspected.

Adult↗

PubMedDate not supplied

Development of real-time polymerase chain reaction assay with TaqMan probe for the quantitative detection of infectious hypodermal and hematopoietic necrosis virus from shrimp.

An assay was developed for the detection of infectious hypodermal and hematopoietic necrosis virus (IHHNV) based on real-time quantitative polymerase chain reaction (PCR). A pair of primers and a TaqMan probe were designed that are specific for the recognition of a conservative region in the IHHNV genome. The IHHNV real-time PCR assay had a detection limit of 9 DNA copies, with a dynamic range of detection between 9 x 106 and 9 DNA copies. The primer pairs and probe were specific to IHHNV and did not cross-react with shrimp genomic DNA or other shrimp viruses such as White Spot Syndrome Virus (WSSV), Monodon Baculovirus (MBV), and hepatopancreatic parvovirus (HPV). This assay has a broad application for basic and clinical investigations. For clinical samples, the real-time PCR assay detected all the positive samples screened by conventional PCR, which indicated the sensitivity of the real-time assay. The IHHNV real-time PCR assay with high sensitivity, specificity, wide range of detection ability, and simplicity is particularly useful for screening large numbers of specimens and measuring viral loads to monitor the broodstock.

Animals↗