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Biomedical subjects

Hong Zhang

Publications and source records attributed to Hong Zhang.

At least 289 records · Page 16Linked to original sources

Spam1 (PH-20) expression in the extratesticular duct and accessory organs of the mouse: a possible role in sperm fluid reabsorption.

A widely conserved sperm antigen, the sperm adhesion molecule 1 (SPAM1 or PH-20) is a glycosylphosphatidyl inositol-linked protein with multiple roles in mammalian fertilization. It has been shown to be dually expressed in testis and epididymis and this is conserved in the four species (mouse, rat, macaques, humans) that have been studied to date. Here, we report Spam1 RNA and protein expression in the murine vas deferens and efferent ducts. In situ hybridization and immunohistochemistry indicate that transcript and protein are distributed in the nonciliated epithelial cells and that the efferent ducts have the most intense staining of all three regions of the excurrent ducts. Spam1 products were also present in the accessory organs, the prostate, and seminal vesicles and its fluid. Using hyaluronic acid substrate gel electrophoresis, hyaluronidase activity at pH 7.0 was detected in the vas deferens but was absent from the efferent ducts, the prostate, and the seminal vesicles/fluid. This suggests that Spam1 may play a nonenzymatic role in these organs. In the efferent ducts, where Spam1 is enriched in the apical (but not basolateral) membrane of nonciliated cells, it is likely to play a role in sperm concentration, which is the established function of that organ.

Animals↗

Targeting multiple signal transduction pathways through inhibition of Hsp90.

The multichaperone heat shock protein (Hsp) 90 complex mediates the maturation and stability of a variety of proteins, many of which are crucial in oncogenesis, including epidermal growth factor receptor (EGF-R), Her-2, AKT, Raf, p53, and cdk4. These proteins are referred to as "clients" of Hsp90. Under unstressed conditions these proteins form complexes with Hsp90 and the cochaperones to attain their active conformations or enhance stability. Inhibition of Hsp90 function disrupts the complex and leads to degradation of client proteins in a proteasome-dependent manner. This results in simultaneous interruption of many signal transduction pathways pivotal to tumor progression and survival. Based on the unique role of the Hsp90 complex, extensive effort has been made in identifying Hsp90 inhibitors. Several compounds have been shown to inhibit Hsp90 in vitro and in vivo and the most advanced, 17-allylamino-17-demethoxygeldanamycin (AAG), is in phase I/II clinical trials. Recent findings with 17-AAG indicate that tumor cells utilize Hsp90 quite differently from normal cells, explaining the selectivity of the drug and suggesting a central role of Hsp90 in malignant progression. Thus these small molecule inhibitors have proved not only to be of great value in identifying new Hsp90 client proteins and in understanding the biology of Hsp90 but are also promising therapeutics in a variety of tumors.

Animals↗

Converged quantum calculations of HO2 bound states and resonances for J=6 and 10.

Bound and resonance states of HO(2) are calculated quantum mechanically using both the Lanczos homogeneous filter diagonalization method and the real Chebyshev filter diagonalization method for nonzero total angular momentum J=6 and 10, using a parallel computing strategy. For bound states, agreement between the two methods is quite satisfactory; for resonances, while the energies are in good agreement, the widths are in general agreement. The quantum nonzero-J specific unimolecular dissociation rates for HO(2) are also calculated.

Journal Article↗

Spatiotemporal chaos control with a target wave in the complex Ginzburg-Landau equation system.

An effective method for controlling spiral turbulence in spatially extended systems is realized by introducing a spatially localized inhomogeneity into a two-dimensional system described by the complex Ginzburg-Landau equation. Our numerical simulations show that with the introduction of the inhomogeneity, a target wave can be produced, which will sweep all spiral defects out of the boundary of the system. The effects exist in certain parameter regions where the spiral waves are absolutely unstable. A theoretical explanation is given to reveal the underlying mechanism.

Journal Article↗

Detection of K-ras point mutation and telomerase activity during endoscopic retrograde cholangiopancreatography in diagnosis of pancreatic cancer.

AIM: To study the value of monitoring K-ras point mutation at codon 12 and telomerase activity in exfoliated cells obtained from pancreatic duct brushings during endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of pancreatic cancer. METHODS: Exfoliated cells obtained from pancreatic duct brushings during ERCP were examined in 27 patients: 23 with pancreatic cancers, 4 with chronic pancreatitis. K-ras point mutation was detected with the polymerase chain reaction and restriction fragment-length polymorphism (PCR-RFLP). Telomerase activity was detected by PCR and telomeric repeat amplification protocol assay (PCR-TRAP-ELISA). RESULTS: The telomerase activities in 27 patients were measured in 21 exfoliated cell samples obtained from pancreatic duct brushings. D450 value of telomerase activities in pancreatic cancer and chronic pancreatitis were 0.446+/-0.27 and 0.041+/-0.0111, respectively. Seventy-seven point eight percent (14/18) of patients with pancreatic cancer and none of the patients with chronic pancreatitis showed telomerase activity in cells collected from pancreatic duct brushings when cutoff value of telomerase activity was set at 2.0. The K-ras gene mutation rate (72.2%) in pancreatic cancer was higher than that in chronic pancreatitis (33.3%) (P<0.05). In considering of both telomerase activities and K-ras point mutation, the total positive rate was 83.3%(15/18), and the specificity was 100%. CONCLUSION: Changes of telomerase activities and K-ras point mutation at codon 12 may be an early event of malignant progression in pancreatic cancer. Detection of telomerase activity and K-ras point mutation at codon 12 may be complementary to each other, and is useful in diagnosis of pancreatic cancer.

Adult↗

SUMO modification is required for in vivo Hox gene regulation by the Caenorhabditis elegans Polycomb group protein SOP-2.

Post-translational modification of proteins by the ubiquitin-like molecule SUMO (sumoylation) regulates their subcellular localization and affects their functional properties in vitro, but the physiological function of sumoylation in multicellular organisms is largely unknown. Here, we show that the C. elegans Polycomb group (PcG) protein SOP-2 interacts with the SUMO-conjugating enzyme UBC-9 through its evolutionarily conserved SAM domain. Sumoylation of SOP-2 is required for its localization to nuclear bodies in vivo and for its physiological repression of Hox genes. Global disruption of sumoylation phenocopies a sop-2 mutation by causing ectopic Hox gene expression and homeotic transformations. Chimeric constructs in which the SOP-2 SAM domain is replaced with that derived from fruit fly or mammalian PcG proteins, but not those in which the SOP-2 SAM domain is replaced with the SAM domains of non-PcG proteins, confer appropriate in vivo nuclear localization and Hox gene repression. These observations indicate that sumoylation of PcG proteins, modulated by their evolutionarily conserved SAM domain, is essential to their physiological repression of Hox genes.

Animals↗

Anterior vertebral body screw position placed thoracoscopically: a function of anatomy and surgeon experience in a porcine model.

STUDY DESIGN: Manual digital measurements, in a porcine model of thoracoscopic anterior instrumentation, divided into two studies: 1) comparing the actual screw position within each vertebra with the perceived ideal screw position and correlation with the learning curve of the surgeon; and 2) a quantitative analysis of the vertebral bodies from T3 to T12 to determine the ideal screw insertion point and trajectory. OBJECTIVE: To investigate whether the position of thoracoscopically placed screws is related to the portion of the thoracic spine instrumented and to the experience of the surgeon and to define the ideal starting position and direction of anterior thoracic screws in a porcine model. SUMMARY OF BACKGROUND DATA: Anterior screw insertion using a thoracoscopic approach is generally considered to be technically demanding and potentially dangerous. To our knowledge, there is no study analyzing the proper position of anterior vertebral screws using thoracoscopic technique and no study analyzing the ideal starting position of anterior vertebral body screws. METHODS: In Study 1, 26 pigs were assigned to two groups (early experience, n = 16; late experience, n = 10) and underwent thoracoscopic anterior instrumentation and fusion from T5 to T10. The screw position was determined in the sagittal plane and in the frontal plane, respectively. In Study 2, 10 thoracic pig spines (T3-T12) were obtained. Each vertebra was digitally measured in the midtransverse plane. Using a point directly adjacent to the rib head as the assumed ideal screw starting point, the percent of vertebral body "obscured" by the rib head and the maximum safe anterior and posterior screw insertion angles were determined. RESULTS: In Study 1, screw positions of Group 1 were significantly more anterior from T5 to T7 compared with the ideal screw position (P < 0.05). Most screws were in the ideal position in Group 2. In both groups, the screw position within T5 was too inferior (P < 0.05). The majority of posterior cortical disruptions occurred in the distal vertebrae. Most anterior disruptions occurred in the proximal vertebrae. In Study 2, the percent of vertebral body behind the rib head significantly decreased from T3 (61.5%) to T12 (25.7%) (P < 0.0001). The maximum anterior insertion angle significantly increased from T3 (11 degrees) to T12 (24 degrees) (P < 0.0001) while the maximum posterior insertion angle significantly decreased from T3 (28 degrees) to T12 (11 degrees) (P < 0.0001). CONCLUSIONS: The position of thoracoscopically placed vertebral screws is dependent on the level of the spine instrumented and surgeon experience. Screws placed in the proximal thoracic spine tend to be too anterior and too inferior while posterior placement of screws occurs in the distal thoracic spine. When using the rib head as the starting point for anterior screw insertion, a slight anterior angle is required in the distal thoracic spine while a slight posterior insertion angle is required in the proximal thoracic spine. A learning curve does exist, however; the proximal screw positioning continues to be a challenge.

Animals↗

Comparison of 11C-choline PET and FDG PET for the differential diagnosis of malignant tumors.

We prospectively assessed and compared the usefulness of 11C-choline positron emission tomography (PET) with that of [18F]-2-fluoro-2-deoxy-D-glucose (FDG) PET for the differentiation between benign and malignant tumors. A total of 126 patients with 130 lesions were studied (25 brain tumors, 51 head and neck tumors, 15 bone tumors, 16 lung tumors, and 23 soft tissue tumors). 11C-choline PET and FDG PET were performed from 5 and 40 min, respectively, after injection of 275-370 MBq tracer. PET data were evaluated using the standardized uptake value (SUV) and were analyzed in accordance with the pathologic data. The 11C-choline uptake in malignancies was 3.9+/-2.3 (n=81), which was significantly higher than that in benign lesions (n=49) (2.6+/-1.7, P<0.005). The FDG uptake in malignancies was 5.9+/-3.8 (n=81) and was also significantly higher than that in benign lesions (2.8+/-2.0, P<0.0001). The 11C-choline uptake in the lesions correlated with FDG uptake (r=0.65, P<0.003). According to an ROC analysis, the areas under the ROC curves (AUCs) for 11C-choline PET were more than 0.8 in bone, head and neck, lung, and soft tissue tumors, while the AUC was 0.79 in brain tumors. The AUCs for FDG PET were similarly more than 0.8 in bone, head and neck, lung, and soft tissue tumors, but had a lower value of 0.585 in brain tumors. In brain, head and neck, bone, and soft tissue tumors, 11C-choline showed higher contrast than FDG. In conclusion, it is feasible to use 11C-choline PET for differentiation between malignant and benign tumours, especially of the brain, head and neck, bone, and soft tissue. However, attention needs to be drawn to the high uptake of 11C-choline in some benign tumors and tumour-like lesions, as this will be of significance in clinical practice.

Adolescent↗

[(11)C]methionine positron emission tomography and survival in patients with bone and soft tissue sarcomas treated by carbon ion radiotherapy.

PURPOSE: The development of the novel carbon ion radiotherapy (CIRT) in the treatment of refractory cancers has resulted in the need for a way to accurately evaluate patient prognosis. We evaluated whether L-[methyl-(11)C]-methionine (MET) uptake and its change after CIRT were the early survival predictors in patients with unresectable bone and soft tissue sarcomas. EXPERIMENTAL DESIGN: MET positron emission tomography was prospectively performed in 62 patients with unresectable bone and soft tissue sarcomas before and within 1 month after CIRT. Tumor MET uptake was measured with the semiquantitative tumor:nontumor ratio (T/N ratio). The MET uptake in the tumor and relevant clinical parameters were entered into univariate and multivariate survival analysis. RESULTS: The overall median survival time was 20 months. Patients with a baseline T/N ratio of 6 (2-year survival rate: 69.4% versus 32.3%; P = 0.01). Patients with a post-CIRT ratio of 4.4 (2-year survival rate: 63.7% versus 41.3%; P = 0.01). A significant higher survival rate was observed in patients with post-therapeutic MET uptake change of >30% than patients in lower change group (2-year survival rate: 74.6% versus 41.6%; P = 0.049). The multivariate analysis showed that both baseline and post-CIRT T/N ratio were statistically significant independent predictors of patient survival. Tumors with larger T/N ratio had a significantly poorer prognosis. CONCLUSIONS: MET uptake as measured by either baseline or post-CIRT T/N ratio was an independent predictor of survival in patients with bone and soft tissue sarcomas treated by carbon ion radiotherapy, whereas post-therapeutic MET uptake change might have potential value for the same purpose.

Adolescent↗

Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor receptor type 2.

Semaphorins, originally identified as axon guidance facto s in the nervous system, play integral roles in organogenesis. Here, we demonstrate a critical involvement of Sema6D in cardiac morphogenesis. Ectopic expression of Sema6D o RNA interference against Sema6D induces expansion or narrowing of the ventricular chamber, respectively, during chick embryonic development. Sema6D also exerts region-specific activities on cardiac explants, a migration-promoting activity on outgrowing cells from the conotruncal segment, and a migration-inhibitory activity on those from the ventricle. Plexin-A1 mediates these activities as the major Sema6D-binding receptor. Plexin-A1 forms a receptor complex with vascular endothelial growth factor receptor type 2 in the conotruncal segment or with Off-track in the ventricle segment; these complexes are responsible for the effects of Sema6D on the respective regions. Thus, the differential association of Plexin-A1 with additional receptor components entitles Sema6D to exert distinct biological activities at adjacent regions. This is crucial for complex cardiac morphogenesis.

Animals↗

Determination of the role of the human RNase H1 in the pharmacology of DNA-like antisense drugs.

Although ribonuclease H activity has long been implicated as a molecular mechanism by which DNA-like oligonucleotides induce degradation of target RNAs, definitive proof that one or more RNase H is responsible is lacking. To date, two RNase H enzymes (H1 and H2) have been cloned and shown to be expressed in human cells and tissues. To determine the role of RNase H1 in the mechanism of action of DNA-like antisense drugs, we varied the levels of the enzyme in human cells and mouse liver and determined the correlation of those levels with the effects of a number of DNA-like antisense drugs. Our results demonstrate that in human cells RNase H1 is responsible for most of the activity of DNA-like antisense drugs. Further, we show that there are several additional previously undescribed RNases H in human cells that may participate in the effects of DNA-like antisense oligonucleotides.

Adenoviridae↗

[The experimental study of histomorphology and biomechanical of cortical strut allograft in proximal femoral].

OBJECTIVE: To explore the deep-frozen allograft strut in the rabbits for the sake of finding some evidence to support the clinical practice of cortical strut allograft. METHODS: Fifty deep-frozen allograft struts were implanted on the lateral side of the femur in 50 male New Zealand white rabbits. These rabbits were randomly divided into 5 groups. The specimen were retrieved at 2, 4, 8, 16, 24 weeks after surgeries. In each group histomorphology and biomechanic properties were studied. RESULTS: From the X ray photography the edge of the strut would turn blunt at the 4th week, union could be found at the 8th week, the inner side of the strut could be absorbed at the 24th week. In the early stage when the strut was implanted in the rabbit, the capillary would be found to grow into the cortical strut from the interior side of it. Then the capillaries were found to converge at the 16th week. This phenomenon is correspondent with the resorption of the dead bone and formation of the new bone. There are few neoformated capillaries on the lateral side of the strut. From the decalcificied section, allograft struts were found to unit to the host at 4 to 8th week. Osteoclast and the new bone formation could be seen at the 8th week, and 3% of the total area of what had been the allograft was replaced by the new bone at that time, 12% was replaced at the 16th week, 21% at the 24th week. There are few resorption or neoformated bone at the lateral side of the strut. The biomechanical property indicated that the strength of the strut decreased at the early time, and only 38% of its original strength remained at 16 weeks. CONCLUSIONS: The cortical allograft strut can unit to the host by the callus. The capillaries invading into the allograft from the interior side, new bone is formed from the interior side. The biomechanical strength of the strut decreased at early stage.

Animals↗

Full S matrix calculation via a single real-symmetric Lanczos recursion: the Lanczos artificial boundary inhomogeneity method.

We present an efficient and robust method for the calculation of all S matrix elements (elastic, inelastic, and reactive) over an arbitrary energy range from a single real-symmetric Lanczos recursion. Our new method transforms the fundamental equations associated with Light's artificial boundary inhomogeneity approach from the primary representation (original grid or basis representation of the Hamiltonian or its function) into a single tridiagonal Lanczos representation, thereby affording an iterative version of the original algorithm with greatly superior scaling properties. The method has important advantages over existing iterative quantum dynamical scattering methods: (a) the numerically intensive matrix propagation proceeds with real symmetric algebra, which is inherently more stable than its complex symmetric counterpart; (b) no complex absorbing potential or real damping operator is required, saving much of the exterior grid space which is commonly needed to support these operators and also removing the associated parameter dependence. Test calculations are presented for the collinear H+H(2) reaction, revealing excellent performance characteristics.

Journal Article↗

Cytoplasmic localization during testicular biogenesis of the murine mRNA for Spam1 (PH-20), a protein involved in acrosomal exocytosis.

The Sperm Adhesion Molecule1 (SPAM1) is the most widely conserved sperm antigen with important roles in mammalian fertilization. Light and electron microscopy were used to localize, by in situ hybridization, the cellular and subcellular sites of Spam1 mRNA in the murine testis. Transcripts were first detected in step 3 round spermatids, gradually increased until step 8 and abruptly decreased between steps 9-11. They were predominantly localized near the ER and were not dispersed throughout the cytoplasm. Immunohistochemistry revealed that Spam1 is present on both the head and tail of sperm in the seminiferous tubules, and provided support for transcriptional regulation of its transcript. Immunocytochemistry confirmed the location of Spam1 on the tail of testicular sperm and demonstrated that it is localized to both the principal piece and the midpiece. Spam1 on epididymal sperm is localized to the midpiece of the tail and changes from a uniform distribution on the head in the caput to a regionalized pattern, first on the posterior and then on the anterior head, in caudal sperm. Spam1 on the surface of caudal sperm was shown to mediate the increase in acrosome reactions induced by the synergistic effects of HA and progesterone, as confirmed in sperm from the Rb(6.16) translocation-bearing mice which are Spam1 mutants. The similar response of human and mouse sperm to these agonists of the acrosome reaction, underscores the usefulness of the mouse as a model to study physiological aspects of SPAM1 in humans where, unlike the mouse, it is the only sperm hyaluronidase.

Acrosome↗

An optimized gossypol high-performance liquid chromatography assay and its application in evaluation of different gland genotypes of cotton.

A comparative study on gossypol content of various genetic types of pigment glands of cotton varieties was conducted through an optimized high-performance liquid chromatography (HPLC) on a C18 column (4.6 mm x 250 mm, 5 microm particle) with methanol-0.5% acetic acid aqueous solution, 90 : 10 (v/v), as mobile phase, at a flow rate of 0.8 ml/min and UV detection at 254 nm. The method was shown to be highly reproducible, with precision [as relative standard deviation (RSD)] and accuracy [as relative mean error (RME)] < 10%, both intra-day and inter-day. Absolute recoveries were > 94%. The results revealed major differences among the different gland varieties or species of cotton, including the special and ordinary glandless and glanded Gossypium hirsutum, G. barbadense, and displayed the precious resources of different glands of extraordinary cotton.

Calibration↗

Effect of CD44 suppression by antisense oligonucleotide on attachment of human trabecular meshwork cells to HA.

The effects of suppression of CD44 by CD44-specific antisense oligonucleotide on attachment of human trabecular meshwork cells to hyaluronic acid (HA) were observed and the possible relationship between CD44 and primary open-angle glaucoma (POAG) investigated. CD44-specific antisense oligonucleotide was delivered with cationic lipid to cultured human trabecular meshwork cells. The expression of CD44 suppressed by CD44-specific antisense oligonucleotide was detected by RT-PCR and Western blotting. The effect of CD44 suppression by specific antisense oligonucleotide on attachment of trabecular meshwork cells to HA was measured by MTT assay. Results showed that expression of CD44 was suppressed by CD44-specific antisense oligonucleotide. Antisense oligonucleotide also suppressed the adhesion of human trabecular meshwork cells to HA in a concentration dependent manner. It was concluded that attachment of human trabecular meshwork cells to HA was decreased when CD44 was suppressed by specific antisense oligonucleotide. CD44 might play a role in pathogenesis of POAG by affecting the adhesion of trabecular meshwork cells to HA.

Cell Adhesion↗

Effects of vascular endothelial cell growth factor on fibrovascular ingrowth into rabbits hydroxyapatite orbital implant.

The effects of different concentrations of vascular endothelial cell growth factor (VEGF) on the fibrovascular ingrowth into rabbits hydroxyapatite orbital implant were investigated. Twelve New Zealand white rabbits were divided into 3 groups and received hydroxyapatite orbital implant surgery in their right eyes. Before and after the operation, the implants were treated with 10 ng/ml VEGF, 100 ng/ml VEGF, or normal saline as control group. The animals received technetium bones scan at 2, 4, and 6 weeks postoperatively. The mean radioactivity counts within region of interest (ROI) of the surgery eye (R) and the non-surgery eye (L) in the same animal were tested, and the R/L ratios were calculated. The implants were harvested at 6th weeks and examined histopathologically. The results showed that at second week, there was no significant difference in mean R/L ratios between VEGF group and control group (F=2.83, P=0.111); At 4th week (F=7.728, P=0.011) and 6th week (F=7.831, P=0.011) postoperatively, the mean ratios in VEGF groups were significantly higher than that in control group. At 6th week postoperatively, the fibrovascularization rates in VEGF groups were higher than in control group significantly (F=8.711, P=0.008). It was suggested that VEGF could promote the fibrovascular ingrowth into hydroxyapatite orbital implant, thus might shorten the time required for complete vascularization of the HA orbital implant.

Animals↗

Existence of heme oxygenase-carbon monoxide-cyclic guanosine monophosphate pathway in human trabecular meshwork cells in vitro.

To confirm the existence of heme oxygenase (HO)- carbon monoxide (CO)- cyclic guanosine monophosphate (cGMP) pathway in the cultured human trabecular meshwork cells (HT-MCs) in vitro, and to evaluate the inductive role of hemin on this pathway, HTMCs of the third to fourth generation were cultured in vitro. Reverse transcripase-polymerase chain reaction (RT-PCR) was employed for detection of HO-1 and HO-2 mRNA. Immunohistochemical staining was used to detect HO-1 and HO-2 proteins. Hemin was added into the culture solution. The HO-1 mRNA levels were quantified by RT-PCR. The relative amount of carbon monoxide released into the media was measured with the quantifying carbon monoxide hemoglobin (HbCO) by spectrophotometry. Radioimmunoassay was used to determine changes of cGMP in HTMCs. The results showed that cultured cells had the specific characteristics of HTMCs. Both HO-1 and HO-2 genes were expressed in HTMCs, as well as HO-1 and HO-2 proteins in HTMCs. Hemin induced HO-1 mRNA, HbCO and cGMP in a dose-dependent manner. In conclusion, HO-CO-cGMP pathway exists in the cultured HTMCs and can be induced by hemin. Pharmacological stimulation of HO-CO-cGMP pathway may constitute a novel therapeutic approach to rescuing glaucoma.

Carbon Monoxide↗