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Hong Zhang

Publications and source records attributed to Hong Zhang.

At least 487 records · Page 27Linked to original sources
PubMed2002

Identification of an organelle receptor for myosin-Va.

Little is known about how molecular motors bind to their vesicular cargo. Here we show that myosin-Va, an actin-based vesicle motor, binds to one of its cargoes, the melanosome, by interacting with a receptor-protein complex containing Rab27a and melanophilin, a postulated Rab27a effector. Rab27a binds to the melanosome first and then recruits melanophilin, which in turn recruits myosin-Va. Melanophilin creates this link by binding to Rab27a in a GTP-dependent fashion through its amino terminus, and to myosin-Va through its carboxy terminus. Moreover, this latter interaction, similar to the ability of myosin-Va to colocalize with melanosomes and influence their distribution in vivo, is absolutely dependent on the presence of exon-F, an alternatively spliced exon in the myosin-Va tail. These results provide the first molecular description of an organelle receptor for an actin-based motor, illustrate how alternate exon usage can be used to specify cargo, and further expand the functional repertoire of Rab GTPases and their effectors.

Adaptor Proteins, Signal Transducing↗
PubMed2002

An ankyrin repeat-containing protein plays a role in both disease resistance and antioxidation metabolism.

The Arabidopsis ankyrin repeat-containing protein AKR2 was identified as a GF14(lambda)-interacting protein in a yeast two-hybrid screening (GF14(lambda) is a 14-3-3 protein). Reduced expression of AKR2 by using the antisense technique results in small necrotic areas in leaves accompanied by higher production of H2O2, similar to the hypersensitive response to pathogen infection in plant disease resistance. Transcripts of genes encoding pathogen-induced protein PR-1 (pathogen-related protein 1) and stress-responsive protein GST6 (glutathione S-transferase 6) are increased in antisense plants. The resistance to a bacterial pathogen infection was also increased by at least 10-fold in antisense plants. AKR2 also interacts with another GF14(lambda)-interacting protein, the ascorbate peroxidase 3 that scavenges H2O2 in plant cells. These data suggest that AKR2 may be a negative regulator of PR-1 expression, and is probably involved in the regulation of antioxidation metabolism that is shared by both disease resistance and stress responses.

Amino Acid Sequence↗
PubMed2002

Notch signaling is involved in the regulation of Id3 gene transcription during Xenopus embryogenesis.

During Xenopus embryogenesis, XId3, a member of the Id helix-loop-helix protein family, is expressed in a large variety of differentiating tissues including epidermis, cement gland, brain, neural tube, neural crest cell derivatives, somites, and tailbud. Transcription of XId3 is mediated by several cis-regulatory elements including an enhancer of 440 bp located 870 bp upstream from the transcription initiation site. The enhancer activity in embryos was studied using transgenic methodology. A galactosidase reporter gene, driven by a regulatory element composed of the enhancer and a minimal promoter derived from the XId3 gene, was expressed in transgenic embryos with a profile that faithfully reproduced that of the endogenous XId3 gene. The pattern resulted from a synergistic effect between the enhancer and the promoter, and in vitro transactivation assays showed that transcription can be stimulated by Notch signaling. The presence of potential Su(H) binding sites, in both the enhancer and the promoter, suggests that these represent candidates for in vivo cis-regulatory elements. The data presented here suggest that Notch control of differentiation may involve activation of transcription of Id, a negative regulator of bHLH transcription factors.

Amino Acid Sequence↗
PubMed2002

Structural basis for the inhibitory efficacy of efavirenz (DMP-266), MSC194 and PNU142721 towards the HIV-1 RT K103N mutant.

The K103N substitution is a frequently observed HIV-1 RT mutation in patients who do not respond to combination-therapy. The drugs Efavirenz, MSC194 and PNU142721 belong to the recent generation of NNRTIs characterized by an improved resistance profile to the most common single point mutations within HIV-1 RT, including the K103N mutation. In the present study we present structural observations from Efavirenz in complex with wild-type protein and the K103N mutant and PNU142721 and MSC194 in complex with the K103N mutant. The structures unanimously indicate that the K103N substitution induces only minor positional adjustments of the three inhibitors and the residues lining the binding pocket. Thus, compared to the corresponding wild-type structures, these inhibitors bind to the mutant in a conservative mode rather than through major rearrangements. The structures implicate that the reduced inhibitory efficacy should be attributed to the changes in the chemical environment in the vicinity of the substituted N103 residue. This is supported by changes in hydrophobic and electrostatic interactions to the inhibitors between wild-type and K103N mutant complexes. These potent inhibitors accommodate to the K103N mutation by forming new interactions to the N103 side chain. Our results are consistent with the proposal by Hsiou et al. [Hsiou, Y., Ding, J., Das, K., Clark, A.D. Jr, Boyer, P.L., Lewi, P., Janssen, P.A., Kleim, J.P., Rosner, M., Hughes, S.H. & Arnold, E. (2001) J. Mol. Biol. 309, 437-445] that inhibitors with good activity against the K103N mutant would be expected to have favorable interactions with the mutant asparagines side chain, thereby compensating for resistance caused by stabilization of the mutant enzyme due to a hydrogen-bond network involving the N103 and Y188 side chains.

Acetophenones↗
PubMed2002

Caenorhabditis elegans unc-37/groucho interacts genetically with components of the transcriptional mediator complex.

Groucho functions as a general corepressor by modulating chromatin structure and has a widespread role in many developmental processes. Here we show that Groucho may also interact with the basal transcriptional machinery. Mutations in Caenorhabditis elegans groucho interact with mutations in components of the transcriptional Mediator complex, resulting in synthetic lethality and loss of male sensory neurons.

Animals↗
PubMed2002

The effect of hemorrhagic shock in a caprine tibial fracture model.

OBJECTIVES: The purpose of this study was to assess effects of hemorrhagic shock on fracture healing in a large animal closed fracture model. DESIGN: Prospective randomized trial. SETTING: University Medical Center. STUDY SUBJECTS: Eight skeletally mature neutered male goats. INTERVENTION: Standardized bilateral closed midshaft tibia fractures were created in all the goats. The goats were randomized to a hemorrhage, shock and resuscitation group (shock group), or a control group. Hemorrhagic shock was induced in the four goats in the shock group. The shock state was maintained for thirty minutes. The remaining four goats were used as a control group. All fractures were stabilized with a standardized external fixator. OUTCOME MEASURES: Swan-Ganz catheters were used to record cardiac output (CO). Arterial blood was sampled to determine base deficit values for the goats after hemorrhage. Radiographs were obtained weekly. After four weeks the tibias were harvested and nondestructively tested in torsion. Immediately after mechanical testing, the tibias were processed for histologic analysis. Standard histomorphologic indices, including total bone volume (TV/BV%), osteoblast surfaces (Ob/BS%), and osteoid surface (OS/BS%), were measured. RESULTS: One goat in the shock group became agitated upon emergence from anesthesia and dislodged two of his external fixator pins. This animal was killed and was not included in the analysis of results. One goat that would have been entered into the control group was then switched to the shock group, leaving four goats in the shock group and three in the control group. One goat in the shock group developed a nonunion of his left tibia fracture. This nonunion occurred because of loosening of pin fixation in the distal tibia. The nonunited bone was not included in the analysis of results. The animal's right tibia healed uneventfully. Hemorrhage uniformly resulted in shock. In the shock group goats, average CO on induction of anesthesia was 3.7 l/min. Average CO dropped to 0.7 after hemorrhage and rose to 6.6 after fluid resuscitation. The average base deficit for the shock group animals was -9.9. The control group animals had minor drops in average CO, from 4.5 on induction of anesthesia to 4.3 on emergence from anesthesia. Radiographic analysis showed no apparent differences in healing between groups when comparing callus area and density. With the exception of the nonunion, all tibiae were considered to be healing normally radiographically. Biomechanical testing showed no statistical difference between the shock and control groups in maximum torque (p = 0.95), stiffness (p = 0.64), and energy absorbed at failure (p = 0.91). Histomorphologic results indicated there were no differences between groups. Shock did not appear to influence bone formation rate or callus remodeling compared with controls (p = 0.6). No evidence of osteocyte necrosis was observed. CONCLUSIONS: In this study no significant difference was found between the shock and control groups in any of the parameters measured. Transient hemorrhagic shock does not appear to adversely affect closed tibia fracture healing in a goat model.

Animals↗
PubMed2002

Overexpression of cyclooxygenase-2 correlates with advanced stages of colorectal cancer.

OBJECTIVE: We aimed to investigate the associations of cyclooxygenase-2 (COX-2) with pathological features and survival in patients with colorectal cancer. METHODS: The expression of COX-2 was examined by immunohistochemistry in 112 primary colorectal cancers, with 64 samples from the corresponding normal mucosa and 16 metastases in the regional lymph nodes of patients with colorectal cancer. The associations of COX-2 expression with clinicopathological features, including survival, were analyzed. RESULTS: The frequency and intensity of COX-2 staining were remarkably increased from the normal samples (17%) to the primary tumors (72%) and to the metastases (100%). Expressions of COX-2 were 25%, 74%, 78%, and 67% in Dukes' A, B, C, and D tumors, respectively (p = 0.005), and positively related to proliferative activity (p = 0.003). COX-2 expressions were 80% in colonic tumors and 60% in rectal tumors (p = 0.03). The expression of COX-2 was positively related to the better differentiated tumors in the colon (p = 0.04). We were unable to find any relationship of COX-2 with patient age, sex, tumor growth pattern, apoptosis, and patient survival (p > 0.05). CONCLUSION: We found that the expression of COX-2 was upregulated from normal cells to primary tumors and to metastases, and related to proliferative activity, tumor location, Dukes' stage, and differentiation. These results further support the evidence that COX-2 may be involved in tumorigenesis and development of colorectal cancer.

Adenocarcinoma↗
PubMed2002

Enzymes of the SUMO modification pathway localize to filaments of the nuclear pore complex.

SUMOs are small ubiquitin-related polypeptides that are reversibly conjugated to many nuclear proteins. Although the number of identified substrates has grown rapidly, relatively little is still understood about when, where, and why most proteins are modified by SUMO. Here, we demonstrate that enzymes involved in the SUMO modification and demodification of proteins are components of the nuclear pore complex (NPC). We show that SENP2, a SUMO protease that is able to demodify both SUMO-1 and SUMO-2 or SUMO-3 protein conjugates, localizes to the nucleoplasmic face of the NPC. The unique amino-terminal domain of SENP2 interacts with the FG repeat domain of Nup153, indicating that SENP2 associates with the nucleoplasmic basket of the NPC. We also investigated the localization of the SUMO conjugating enzyme, Ubc9. Using immunogold labeling of isolated nuclear envelopes, we found that Ubc9 localizes to both the cytoplasmic and the nucleoplasmic filaments of the NPC. In vitro binding studies revealed that Ubc9 and SUMO-1-modified RanGAP1 bind synergistically to form a trimeric complex with a component of the cytoplasmic filaments of the NPC, Nup358. Our results indicate that both SUMO modification and demodification of proteins may occur at the NPC and suggest a connection between the SUMO modification pathway and nucleocytoplasmic transport.

Active Transport, Cell Nucleus↗
PubMed2002

Assisting functional assignment for hypothetical Heamophilus influenzae gene products through structural genomics.

The three-dimensional structures of Haemophilus influenzae proteins whose biological functions are unknown are being determined as part of a structural genomics project to ask whether structural information can assist in assigning the functions of proteins. The structures of the hypothetical proteins are being used to guide further studies and narrow the field of such studies for ultimately determining protein function. An outline of the structural genomics methodological approach is provided along with summaries of a number of completed and in progress crystallographic and NMR structure determinations. With more than twenty-five structures determined at this point and with many more in various stages of completion, the results are encouraging in that some level of functional understanding can be deduced from experimentally solved structures. In addition to aiding in functional assignment, this effort is identifying a number of possible new targets for drug development.

Genome, Viral↗
PubMed2002

Gestational diabetes mellitus in women of single gravidity in Tianjin City, China.

OBJECTIVE: The aim of this study was to investigate the prevalence of gestational diabetes mellitus (GDM) and risk factors for the development of GDM in pregnant women in Tianjin, China, where the prevalence of GDM is still unknown. STUDY DESIGN AND METHODS: A total of 9,471 pregnant women living in the six urban districts of Tianjin, China, took part in the initial screening between December 1998 and December 1999. The screening test consisted of a 50-g 1-h glucose test. Women with a reading > or =7.8 mmol/l at the initial screening were invited to undergo a 75-g 2-h oral glucose tolerance test (OGTT). GDM was confirmed using the World Health Organization's diagnostic criteria. RESULTS: At the initial screening test, 888 women had a glucose reading of > or =7.8 mmol/l. A total of 701 (79%) women took a subsequent OGTT. Of these, 174 women were confirmed to have GDM (154 with impaired glucose tolerance [IGT] and 20 with diabetes). The prevalence of GDM was 2.31% (2.03% for IGT and 0.28% for diabetes), adjusting for serum glucose levels at the initial screening test. Independent predictors for GDM were maternal age, stature, prepregnancy BMI, weight gain in pregnancy before screening, diabetes in first-degree relatives, and habitual cigarette smoking during pregnancy. Women who smoked or had a short stature are more likely to develop GDM than their counterparts. CONCLUSIONS: The prevalence of GDM in pregnant women in the city of Tianjin, China, was 2.31%. Short stature and smoking in pregnancy were additional risk factors for GDM.

Adult↗
PubMed2002

Women with impaired glucose tolerance during pregnancy have significantly poor pregnancy outcomes.

OBJECTIVE: This article tests the hypothesis that women with impaired glucose tolerance (IGT) have the same pregnancy outcomes as those of their counterparts with normal glucose tolerance. RESEARCH DESIGN AND METHODS: From December 1998 to December 1999, 84 of 90 antenatal care base units (ACBUs) under the Tianjin Antenatal Care Network in China participated in the first screening program for gestational diabetes mellitus (GDM). A total of 9,471 pregnant women under the care of participating ACBUs were screened. Of the women screened, 154 were positive for IGT. Of the 154 women, 102 opted for conventional obstetric care. The comparison group was 302 women of normal glucose tolerance (NGT). The initial screening consisted of a 50-g 1-h glucose test, and was carried out at 26-30 gestational weeks. Women with a serum glucose > or =7.8 mmol/l were followed up with a 75-g 2-h oral glucose tolerance test. The World Health Organization's diagnostic criteria for GDM were used. RESULTS: Women with IGT were at increased risk for premature rupture of membranes (P-ROM) (odds ratio [OR] 10.07; 95% CI 2.90-34.93); preterm birth (6.42; 1.46-28.34); breech presentation (3.47; 1.11-10.84); and high birth weight (90th percentile or 4,000 g) (2.42; 1.07-5.46); adjusting for maternal age, pregravid BMI, hospital levels, and other confounding factors. CONCLUSIONS: The presence of IGT in pregnancy is predictive of poor pregnancy outcomes.

Adult↗
PubMed2002

Clinical and laboratory features of preleukemia patients.

OBJECTIVE: To explore prospective diagnostic criteria for preleukemia. METHODS: A case control study was done comparing the discrepancies on clinical and laboratory features between patients with preleukemia and those with chronic aplastic anemia (CAA) or atypical paroxysmal nocturnal hemoglubinuria (a-PNH). RESULTS: There were eight variables of significance: (1) lymphocytoid micromegakaryocytes in the bone marrow; (2) immature granulocytes in the peripheral blood; (3) > or = 2.0% myeloblasts in the bone marrow; (4) positive periodic acid schiff (PAS) stained nucleated erythrocytes; (5) myeloid differentiation index > or = 1.8; (6) typical colonal karyotypic abnormalities; (7) negative sister chromatid differentiation; (8) cluster/colony ratio of granulocyte-macrophage colony-forming units (CFU-GM) > 4.0. The following criteria were assigned: A: to meet variable one and at least two of the other seven variables and B: to meet at least four of the eight variables. All of the patients with preleukemia met either A or B and none of the patients with CAA or a-PNH did. CONCLUSIONS: Preleukemia is different from CAA or a-PNH. It has its own clinical and laboratory features, which may be useful for its prospective diagnosis.

Adolescent↗
PubMed2002

[Analysis on clinical data of 677 death cases with nasopharyngeal carcinoma].

OBJECTIVE: To study the death causes in 677 patients with nasopharyngeal carcinoma (NPC). METHOD: The clinical data of 677 death cases with NPC hospitalized in our department from 1974 to 1990 were analysed. RESULT: In our data, the ratio of male to female was 4.3:1. The main age stage was from forty to sixty. The pathological type was mostly poorly differentiated squamous cell carcinoma. The cases with stage III-IV disease were account for 81.3%. The patients treated by radiotherapy combined with chemotherapy survived longer than those treated by radiotherapy alone (P < 0.05). The majority of the patients died of distal metastasis (372, 54.9%) and local-regional lymph node uncontrolled (142, 20.9%) after treatment. CONCLUSION: The main death causes of the patients with NPC in our investigation were distal metastasis and local-regional recurrence. The treatment of radiotherapy plus chemotherapy probably increases survival time and reduces the death rate in patients with NPC.

Adolescent↗
PubMed2002

NDPP1 is a novel CARD domain containing protein which can inhibit apoptosis and suppress NF-kappaB activation.

We have identified several novel human caspase recruitment domain (CARD) containing genes. In this report, we describe one among them, NDPP1. The mRNA expression of NDPP1 was higher in the kidney and testis of normal tissues. High expression was also detected in breast cancer, prostate cancer and granulosa tumor cells but not in bladder cancer cells. Transfection experiments demonstrated that NDPP1 was able to supress Bax-induced apoptosis in REF52 cells. Furthermore, NDPP1 is able to inhibit NF-kappaB activation induced by TNF-alpha treatment in HepG2 cells. Our results demonstrated that NDPP1 is a novel member of the CARD family and a negative regulator of cell death and inflammatory response. The NDPP1 locus has been assigned to chromosome 19q13.3. The NDPP1 gene consists of 14 exons and transcribts for at least five splicing variants.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Expression of p16, p27, p53, p73 and Nup88 proteins in matched primary and metastatic melanoma cells.

Cutaneous melanoma is a tumor with high metastatic potential, but the mechanisms leading to progression are still not fully understood. In this study, we examined whether p16, p27, p53, p73 and Nup88 proteins were involved in the progression from primary to metastatic melanomas by immunocytochemistry and Western blotting in eleven melanoma cell lines from five matched primary and metastatic melanomas. We demonstrated that the primary and metastatic melanomas expressed differently p16, p27, p73 and Nup88 proteins. When expressed in the primary melanoma cells p16 and p27 were lost or reduced in almost all the metastatic melanoma cell lines. In contrast, p73 and Nup88 were expressed in most of the tested melanoma cell lines and were increased in the metastatic melanomas. p53 was expressed at the same level in both the primary and metastatic melanoma cells. These data suggest that a reduced expression of p16 and p27 and an enhanced expression of p73 and Nup88 might play an important role in the progression of melanoma from primary tumor to metastasis.

Cell Cycle Proteins↗
PubMed2002

[Protective effect of Ginkgo biloba extract on acute lung injury induced by lipopolysaccharide in D-galactose aging rats].

OBJECTIVE: To investigate the effect of Ginkgo biloba extract (GBE) on acute lung injury(ALI) induced by lipopolysaccharide (LPS) in aging rats. METHODS: The rats were randomly divided into two parts: six rats served as normal controls; 18 rats were used for producing the aging animal model ( D-gal 50 mg/kg body weight was injected intraperitoneally, once a day for 6 weeks). The aging rats were then randomly divided into 3 groups: 6 rats as the aging control group; another 6 as the LPS treated aging group (LPS,5 mg/kg body weight intravenous injection); and the third as the GBE+LPS group (6 rats, GBE was started 7 days before the experiment,given once a day via the esophagus, the amount of flavone glycosides administered being 8 mg/kg body weight, and on the day of experiment, one dose of GBE was given 2 hours before LPS administration ). The samples were collected 2 hours after LPS or saline administration. RESULTS: Compared with normal controls, the SOD activity in red cells and the Na(+) -K(+) -ATPase activity in the lung tissue decreased markedly (all P < 0.05), but the LDH activity increased (P < 0.05) in the aging rats. ALI was observed in the aging rats 2 hours after LPS administration. Compared with the aging control, in the LPS treated rats, there were more inflammatory cells in the lung tissue; protein content in bronchial alveolar lavage fluid (BALF) and the pulmonary permeability index (PPI) increased significantly (all P < 0.001); LD, MDA, NO(2) (-)/NO(3)(-), ET-1 and TNF-alpha content and LDH activity in blood, and MPO activity in lung tissue all increased significantly. On the contrary, SOD activity in red cells and Na(+) -K(+) -ATPase activity in lung tissue decreased markedly (P < 0.05, P < 0.01). These changes, except SOD, were markedly attenuated in the GBE+LPS rats. CONCLUSIONS: The anti-oxidant activity was decreased in D-gal-induced aging rats. Intravenous administration of LPS caused acute lung injury in aging rats. GBE had protective effect on ALI induced by LPS.

Aging↗
PubMed2002

[A long-term follow-up study of 50 patients with severe aplastic anemia who have survived more than 3 years after immunosuppressive therapy].

OBJECTIVE: To evaluate the long-term outcome of immunosuppressive therapy (IST) in patients with severe aplastic anemia (SAA). METHODS: Hematopoietic recovery (peripheral blood cell counts, bone marrow aspirates, bone marrow biopsy, in vitro culture of hematopoietic progenitors), immunity of T lymphocyte, quality of life and side-effects of the therapy were assessed in 50 SAA patients who have survived more than 3 years after IST. RESULTS: At 3 years, 4 years and 5 years follow-up, 81.5% (13 cases), 86.7% (13 cases) and 89.5% (17 cases) of the SAA patients reached and maintained normal peripheral blood cell counts, 93.4% (15 cases), 93.3% (14 cases) and 94.7% (18 cases) showed normal bone marrow pictures, and 37.5% (6 cases), 40.0% (6 cases) and 73.7% (14 cases) had normal yields of bone marrow cell culture, respectively. Overall, 86.0% (43 cases), 94.0% (47 cases) and 52.0% (26 cases) of the total SAA patients were normalized in peripheral blood counts, bone marrow picture and culture of hematopoietic progenitor yields, respectively. During the follow-up, 88.0% (44 cases) of the patients achieved 100 of Karnofsky scores; 26 of the 31 patients (83.9%) who received bone marrow biopsy showed normal histological pictures, and 29 of 37 patients (78.4%) tested had normal subsets of T lymphocytes. No clonal disease was found. The late side-effects of IST were mild. All of the parameters tested were normal in 24 patients. CONCLUSION: After IST, the hematopoietic function of bone marrow, the immunity of the T lymphocyte and the life quality were normalized with few side-effects in patients with SAA. These patients would probably be cured.

Adolescent↗