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Biomedical subjects

Hong Zhang

Publications and source records attributed to Hong Zhang.

At least 127 records · Page 7Linked to original sources
PubMed2006

Identification of new biomarkers for clinical trials of Hsp90 inhibitors.

The selective heat shock protein 90 (HSP90) inhibitor 17-allyamino-17-demethoxygeldanamycin (17-AAG) is currently in phase I/II clinical studies at numerous institutions. Heretofore, the biomarkers to detect 17-AAG bioactivity (Hsp70, Raf-1, and cyclin-dependent kinase 4) had to be analyzed by Western blot of cellular samples, either from tumor biopsies or peripheral blood leukocytes, a method that is both laborious and invasive. We have identified two new biomarkers [insulin-like growth factor binding protein-2 (IGFBP2) and HER-2 extracellular domain] that can be readily detected in patient sera by ELISA. Both secreted proteins are derived from or regulated by Hsp90 client proteins, raising hopes that they might be sensitive serum markers of HSP90 inhibitor activity. Several structurally unrelated HSP90 inhibitors dose-dependently decreased secretion of both IGFBP-2 and HER-2 extracellular domain into culture medium, and both proteins were more sensitive to HSP90 inhibitors than previously identified biomarkers. In sera from BT474 tumor-bearing mice, both IGFBP-2 and HER-2 extracellular domain were down-regulated by 17-AAG in a time-dependent and dose-dependent manner, coincident with the degradation of HER-2 and attenuation of AKT activity in the tumors. Furthermore, IGFBP-2 levels at the end of treatment correlated with residual tumor load, suggesting that IGFBP-2 might serve as an early indicator of therapeutic response. In addition, we also found that both IGFBP-2 and HER-2 extracellular domain levels are elevated in patient sera from several cancer types, suggesting that these novel secreted biomarkers could be valuable pharmacodynamic tools in clinical trials of HSP90 inhibitors.

Animals↗
PubMed2006

Sensitization of B16 tumor cells with a CXCR4 antagonist increases the efficacy of immunotherapy for established lung metastases.

Expression of the chemokine receptor CXCR4 by tumor cells promotes metastasis, possibly by activating prosurvival signals that render cancer cells resistant to immune attack. Inhibition of CXCR4 with a peptide antagonist, T22, blocks metastatic implantation of CXCR4-transduced B16 (CXCR4-luc-B16) melanoma cells in lung, but not the outgrowth of established metastases, raising the question of how T22 can best be used in a clinical setting. Herein, whereas the treatment of CXCR4-luc-B16 cells in vitro with the CXCR4 ligand CXCL12 did not reduce killing induced by cisplatin or cyclophosphamide, CXCL12 markedly reduced Fas-dependent killing by gp100-specific (pmel-1) CD8(+) T cells. T22 pretreatment restored sensitivity of CXCR4-luc-B16 cells to pmel-1 killing, even in the presence of CXCL12. Two immune-augmenting regimens were used in combination with T22 to treat experimental lung metastases. First, low-dose cyclophosphamide treatment (100 mg/kg) on day 5 in combination with T22 (days 4-7) yielded a approximately 70% reduction of B16 metastatic tumor burden in the lungs compared with cyclophosphamide treatment alone (P < 0.001). Furthermore, whereas anti-CTL antigen 4 (CTLA4) monoclonal antibody (mAb; or T22 treatment) alone had little effect on established B16 metastases, pretreatment with T22 (in combination with anti-CTLA4 mAb) resulted in a 50% reduction in lung tumor burden (P = 0.02). Thus, in vitro, CXCR4 antagonism with T22 renders B16 cells susceptible to killing by antigen-specific T cells. In vivo, T22 synergizes with cyclophosphamide or anti-CTLA4 mAb in the treatment of established lung metastases, suggesting a novel strategy for augmenting the efficacy of immunotherapy.

Animals↗
PubMed2006

Visual response properties of retinal ganglion cells in the royal college of surgeons dystrophic rat.

PURPOSE: Alterations in retinal ganglion cell response patterns were profiled in dystrophic Royal College of Surgeons (hereafter RCS) rats over the first 100 postnatal days as a baseline for retinal rescue and vision restoration strategies. This method enabled the evaluation of the extent to which postreceptoral neuronal attributes in degenerating retinas mirror inferred declines in photoreceptor function. METHODS: Single-unit responses from large retinal ganglion cells were recorded from age-matched dystrophic RCS (RCS-rdy(-)) and congenic RCS-p(+) (hereafter wild-type or wt) rats were recorded in vitro under visual control. Cells were profiled with conventional spatial and flux stimulus modulations. RESULTS: Ganglion cell single unit and population attributes alter slowly over the course of photoreceptor degeneration in dystrophic RCS rats, with significant decreases in apparent receptive field size, contrast sensitivity, and threshold sensitivity detected by the first month of life. Spatial frequency tuning and contrast responses were extremely weak by postnatal day (P)76, paralleled by a progressive decline in signal-to-noise (S-N) ratio to roughly unity by postnatal day (P)107. This decline was only a simple loss of responsivity, as background firing rates increased substantially over time. Whereas wt retinas were dominated by ON-center cells (15/23 cells), dystrophic animals were dominated by OFF-center cells by P47 (24/27 cells). CONCLUSIONS: The first definitive signs of degeneration in dystrophic RCS rats are parallel decreases in ganglion cell threshold sensitivity and receptive field size, followed by deterioration in spatial summation. Arguably, these changes can be qualitatively explained as photoreceptor signaling losses. However, the apparent shift in population profile from ON- to OFF-center ganglion cells long before loss of the b-wave at P90 implies that a reactive mechanism such as bipolar cell rewiring and/or transformation of neuronal phenotypes occur during the early phase of photoreceptor stress, before rod and cone death.

Animals↗
PubMed2006

RNA-binding proteins SOP-2 and SOR-1 form a novel PcG-like complex in C. elegans.

We describe the identification and characterization of a novel PcG gene in C. elegans, sor-1, which is involved in global repression of Hox genes. sor-1 encodes a novel protein with an RNA-binding activity. We provide evidence that SOR-1 and the previously identified RNA-binding protein SOP-2 may constitute an RNA-binding complex in Hox gene repression. SOR-1 and SOP-2 directly interact with each other and are colocalized in nuclear bodies. The localization of SOR-1 depends on SOP-2. Surprisingly, homologs of SOR-1 and SOP-2 are not found in other organisms, including the congeneric species C. briggsae, suggesting an unexpected lack of evolutionary constraint on an essential global gene regulatory system.

Amino Acid Sequence↗
PubMed2006

Germ cell loss induced by 12C6+ ion irradiation in young female mice.

The ovaries of Kun-Ming strain mice (3 weeks) were irradiated with different doses of 12C6+ ion in the Bragg peak or the plateau region. At 10th day after irradiation, ovarian and uterine weights were measured; normal and atretic (identified with the oocyte to be degenerating or absent) primordial, primary and preantral follicles were identified in the largest cross-section of each ovary. Percentage (%) of normal follicles of each developmental stage of oogenesis was calculated. The data showed that compared to controls, there was a dose-related decrease in percentage of normal follicles in each developmental stage. And the weights of ovary and uterus were also reduced with doses of irradiation. Moreover, these effects were much more significant in the Bragg peak region and the region close to the Bragg peak than in the beam's entrance (the plateau region). Radiosensitivity varied in different follicle maturation stages. Primordial follicles, which are thought to be extremely sensitive to ionizing irradiation, were reduced by 86.6%, while primary and preantral follicles reduced only by 72.5% and 61.8% respectively, by exposure with 6 Gy of 12C6+ ion in the Bragg peak region and the region close to the Bragg peak. The data suggested that due to their optimal depth-dose distribution in the Bragg peak region, heavy ions are ones of the best particles for radiotherapy of tumors located next of vital organs or/and surrounded by normal tissues, especially radiosensitive tissues such as gonads.

Animals↗
PubMed2006

Bcl-xL and bcl-2 proteins in melanoma progression and UVB-induced apoptosis.

Whether bcl-xL and bcl-2 play an essential role in melanoma progression and UVB-induced apoptosis is not completely understood. We investigated the expression of bcl-xL and bcl-2 in matched primary and metastatic melanoma tumors and melanoma cell lines from the same melanoma patients to clarify the importance of bcl-xL and bcl-2 in melanoma progression and in UVB-induced apoptosis. The expression of bcl-xL and bcl-2 proteins was examined by immunohisto(cyto)chemistry and Western blot in melanoma tumors and melanoma cells. Cellular viability and apoptosis were estimated after the melanoma cells were exposed to 30, 60 and 180 mJ/cm2 UVB. Both primary melanoma tumors and melanoma cells showed lower expression of bcl-xL and bcl-2 proteins estimated as frequency of positive cells than their matched metastatic tumors and cells in vitro. After exposure to UVB, the cell viability decreased and the number of apoptotic cells increased in both primary and metastatic melanoma cell lines. These changes were more pronounced in the primary melanoma cells than in the matched metastatic cells. After UVB exposure, the expression of bcl-xL protein decreased in primary melanoma cells in a dose- and time-dependent manner, but the expression of bcl-2 was not influenced. The expression of bcl-xL and bcl-2 proteins was increased during melanoma progression from primary to metastatic melanoma. Reduction of bcl-xL, but not bcl-2 expression was involved in UVB-induced apoptosis in primary melanoma cells.

Apoptosis↗
PubMed2006

[Study on protective effect of tetrandrine on lipopolysaccharide induced pancreatic acinar cell damage and its mechanism].

OBJECTIVE: To evaluate the protective effect of tetrandrine (Tet) on lipopolysaccharide (LPS)-induced pancreatic acinar cell damage and to explore its mechanism. METHODS: SD male rat's pancreatic acinar cells were isolated by collagenase digestion and they were pre-treated with Tet (50 micromol/L and 100 micromol/L), then exposed to LPS (10 mg/L) or conventional culture medium respectively. At 0, 1, 4, 10 hours after treatment with the agents, cell viability was determined by methyl thiazolyl tetrazolium (MTT), and the supernatant supernate of cells was collected for determination of the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) and phospholipase A(2) (PLA(2)). Some cells were loaded with Fluo-3/AM, and the dynamic change in intracellular Ca(2+) ([Ca(2+)]i) in single pancreatic acinar cell was determined by laser scanning confocal microscopy. RESULTS: Tet attenuated LPS-induced cell damage (P<0.05 and P<0.01) and inhibited the elevation of cytosolic free calcium of rat pancreatic acinar cells. In the supernatant, Tet pretreatment decreased the content of MDA and the activity of PLA(2) and increased the activity of SOD (all P<0.05). CONCLUSION: Tet attenuates LPS-induced cell damage by blocking [Ca(2+)]i overload, inhibiting superoxide response, decreasing activity of pancreatic enzyme, thus it shows a protective effect on pancreatic acinar cells.

Animals↗
PubMed2006

Enhancement of splenic glucose metabolism during acute malarial infection: correlation of findings of FDG-PET imaging with pathological changes in a primate model of severe human malaria.

In the current study, to elucidate the clinical features of severe malaria, we performed whole-body positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) of Plasmodium coatneyi-infected acute-phase Japanese macaques. The infected monkeys clearly exhibited increase in splenic FDG uptake indicating marked enhancement of glucose metabolism. The standardized uptake values (SUVs) of the spleen in the infected monkeys were significantly higher than those in the uninfected monkey. At autopsy, splenomegaly was clearly present in all infected monkeys, and histopathologic findings included hyperplasia of lymphoid follicles in white pulp, a large number of activated macrophage, and congestion of parasitized red blood cells (PRBCs) and malaria pigments in red pulp. We suggest that increase in splenic glucose uptake may thus be closely related to activation of splenic clearance system against blood-stage malarial parasites.

Animals↗
PubMed2006

[Study of cellular electrophysiology based on Noble98 dynamic model of ventricular action potential].

On the basis of mammalian ventricular action potential model Noble98, and with the use of Runge-Kutta for solution, the Wenckebach periodicity phenomenon, the transmural heterogeneity of the ventricular myocardium and its rate dependence are studied. The results indicate that these inherent properties may, lead to temporal-space disorganized in the normal heart,and may become the underlying factors for arrhythmias. At the same time, in this study are established the basic methods for quantitative cellular electrophysiology which is essential for future studies on the mechanism of arrhythmia.

Action Potentials↗
PubMed2006

[Comparison of unconsciousness prediction probability with approximate entropy and bispectral index during sedation].

OBJECTIVE: To compare the unconsciousness prediction probability (Pk) estimated by approximate entropy (ApEn) and bispectral index (BIS) during the sedation produced by target-controlled infusion (TCI) of propofol. METHODS: Twenty patients (ASA class I-II) scheduled for elective lower limb operations under epidural anesthesia were studied. TCI of propofol was initiated at target plasma concentration of 0.5 microg/ml, and increased by 0.3 to 0.5 microg/ml until loss of consciousness, and then decreased until consciousness recovery. Each target plasma concentration of propofol lasted for 12 min. ApEn and BIS were recorded simultaneously during the periods of consciousness and unconsciousness every 3 min. The Pk of unconsciousness with ApEn and BIS were calculated and compared. RESULTS: ApEn was 0.84+/-0.05 in the state of consciousness and 0.71+/-0.06 upon loss of consciousness, and BIS in the corresponding stages were 80.2+/-6.2 and 67.3+/-7.9, respectively. The Pk of unconsciousness between ApEn (Pk=0.97+/-0.06) and BIS (Pk=0.91+/-0.11) did not significantly differ (P>0.05). CONCLUSION: ApEn as well as BIS is acceptable for predicting consciousness and unconsciousness produced by TCI propofol.

Adult↗
PubMed2006

[Computer simulation methods of cardiac electrophysiology].

Computer simulation is one of the powerful protocols to study electrophysiology theoretically. In this paper,the algorithm of Rush and Larsen was used to solve the ordinary differential equations (ODE's) in the Luo-Rudy models of mammalian ventricular cell. The operator splitting and adaptive time step methods were used to solve the partial differential equations (PDE's) in cardiac tissue conduction models. Using these methods we accomplished the simulation programs of single ventricular cell model and two-dimensional (2-D) tissue model. The methods of initiating spiral waves were studied with this software. The data obtained from 2-D simulation can be used for further study on isopotential contour lines, spiral wave tip trajectories, and pseudo-ECG.

Algorithms↗
PubMed2006

[Study on correlated factors and clinical features of fungal rhinosinusitis].

OBJECTIVE: To investigate the correlated factors and clinical features of fungal rhinosinusitis. METHODS: The clinical data of 110 patients with fungal rhinosinusitis treated by surgery and another group of 110 patients with chronic rhinosinusitis who were sampled randomly between January 1999 and June 2004 in our hospital were retrospectively compared. The correlated factors and the clinical features of fungal rhinosinusitis were investigated by using the multiple factor Logistic regression analysis and chi-square test. The pathological types of 110 fungal rhinosinusitis were classified by using Gomori methenamine silver staining which was special for fungi. RESULTS: The logistic regression predictive equation for fungal rhinosinusitis was : y = -8.713 + 0.496x1 + 4.575x2 + 1. 190x3 + 4.119x4 + 1.199x5 + 2. 698x6, P = exp (y)/[1 + exp(y)], in which the concomitant variables were course of the disease (x1), haem-nasal discharge (x2), headache (x3), calcified plaque in CT scan (x4), age (x5) and unilateral/bilateral sinus lesion (x6), respectively. The P value meant the probability of suffering fungal rhinosinusitis. Compared with chronic rhinosinusitis, the clinical features of fungal rhinosinusitis were female, over 40-year-old, course of disease < 3 years, headache, haem-nasal discharge, unilateral sinus lesion and calcified plaque in CT scan. Among the 110 patients with fungal rhinosinusitis, 34 cases were chronic invasive and 76 were non-invasive. CONCLUSIONS: The clinical features of fungal rhinosinusitis are significant for the diagnosis, and it can be predicted by using the suitable logistic predictable equation.

Adolescent↗
PubMed2006

[Relationship between glucocorticoid receptors in the peripheral blood lymphocytes and trabecular meshwork and glucocorticoid induced glaucoma].

OBJECTIVE: To measure the number of glucocorticoid receptors (GR) in the trabecular meshwork and peripheral blood lymphocytes of rabbits, and to explore their relationship with steroid-induced glaucoma. METHODS: Steroid-induced glaucoma model was induced by subconjunctival injection of 0.5 mg dexamethasone in the right eyes every two days for a month. Before the injection, GR concentration was measured in peripheral blood lymphocytes and trabecular meshwork of rabbits using the radio-ligand binding assay. GR concentration was measured again 30 days after the injection. The data was analyzed with SPSS software. RESULTS: The GR concentration in the peripheral blood lymphocytes and the trabecular meshwork of rabbits was (3642 +/- 947) site/cell and (2437.85 +/- 733.93) dmp/mg, respectively. The expression level in lymphocytes was significantly correlated with that in the trabecular (r = 0.862, P < 0.01). After treated with dexamethasone, the intraocular pressure of rabbits increased significantly, and the GR concentration in peripheral blood lymphocytes decreased significantly. Elevating level of IOP correlated positively with the primary and decreasing level of GR (r = 0.78, 0.79, P < 0.01). CONCLUSIONS: GR concentration in the peripheral blood lymphocytes of rabbits can reflect directly the GR number in the trabecular meshwork. There may be a close relationship between the GR number in peripheral blood lymphocytes and steroid-induced glaucoma.

Animals↗
PubMed2006

[Age-related changes serum levels of MMP-1 and MMP-2 in women: their relationship with bone biochemical markers and bone mineral density].

OBJECTIVE: To study the relationship between serum matrix metalloproteinase (MMP)-1, MMP-2 and bone turnover markers, bone mineral density (BMD) in Chinese women aged 20-80 years. METHODS: Serum MMP-1, MMP-2, bone alkaline phosphatase (BAP), osteocalcin (OC) and cross-linked N-telopeptide of collagen type I (NTX) were measured using ELISA. BMD were measured using DEXA in 591 women. RESULTS: (1) MMP-1 and MMP-2 were positively correlated with age (both P < 0.001). (2) Level of MMP-2 in postmenopausal women was significantly higher than that in premenopausal women (P < 0.001). (3) Significant negative relationship was found between MMP-2 and BMD, but multiple linear stepwise regression analysis showed MMP-2 was not the determinant factor of BMD. (4) Positive correlation was found between MMP-2 and BAP, OC, NTX (all P < 0.001). (5) Serum MMP-2 concentrations were significantly higher in postmenopausal osteoporotic women than in age-matched normal controls and osteopenic subjects. CONCLUSION: Circulating MMP-2 and markers of bone turnover are related and they may increase with the increase in bone-turnover. The increase of serum MMP-2 appears possibly as a concomitant event in high bone turnover state such as postmenopausal osteoporosis.

Adult↗
PubMed2006

[Laboratory diagnoses of the first confirmed human case of avian influenza A (H5N1) in the mainland of China].

BACKGROUND: To determine the etiologic agent of an atypical pneumonia human case admitted to Xiangtan City hospital, Hunan Province in Oct. 2005. METHODS: The patient's respiratory tract samples and serum were collected. Throat swabs were tested by microneutralization and hemagglutination-inhibition assays. RESULTS: The results of nucleic acid detection of all respiratory samples were negative and virus isolation was also negative. The H5-specific antibodies of convalescence showed a 4-fold greater rise than acute phase. CONCLUSION: The atypical pneumonias case was confirmed as the first human case of avian influenza A (H5N1) infection in the mainland of China.

Animals↗
PubMed2006

[Two cases report and literature review of IgA nephropathy combined with primary membranous nephropathy].

OBJECTIVE: To describe the clinical and pathological characteristics and prognosis of IgA nephropathy coexisting with membranous nephropathy (MN). METHODS: Two cases were confirmed to have IgA nephropathy as well as primary MN by immunofluorescence and immuno-electron microscopy for renal biopsy and clinical data. Clinical and pathological manifestations were collected and prognosis was investigated. RESULTS: The pathological characteristics included IgA deposit in mesangium but IgG deposit in subepithelial site mainly. Two patients presented moderate to heavy proteinuria, minimal hematuria, and normal renal function. During 9 months of follow up, the renal function remained normal. CONCLUSIONS: The combined form of membranous nephropathy and mesangioproliferative IgA nephropathy was uncommon. The clinical characteristics of the two cases in this study were more similar to those of MN. Coexistence of two kinds of primary glomerulonephritis did not result in a particularly deterioration in clinical outcome.

Adult↗
PubMed2006

[Optical mapping of the membrane potential with voltage-sensitive dyes].

Optical mapping of the membrane potential with voltage-sensitive dyes is an advanced approach that involves in many theories such as molecular photonica, physiology and computer science. Compared with the conventional techniques of membrane patch-clamp and microelectrode, the optical mapping system can measure not only the changes of a single membrane potential from multiple sites simultaneously but also the conduction properties of the cell populations. So this technique provides an important method for studying the electrophysiology of the small cell, the tiny neurite and the cardiac arrhythmia, etc. Because this technique can also avoid the electromagnetic interferences, it uniquely provides an ideal means for studying the mechanisms such as cardiac defibrillation. In this paper the principles and the system structure of the optical mapping are introduced, its applications and future developments are also presented at the same time.

Animals↗