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Biomedical subjects

Zheng Lin

Publications and source records attributed to Zheng Lin.

At least 19 recordsLinked to original sources
PubMed2006

Structure of the protein phosphatase 2A holoenzyme.

Protein Phosphatase 2A (PP2A) plays an essential role in many aspects of cellular physiology. The PP2A holoenzyme consists of a heterodimeric core enzyme, which comprises a scaffolding subunit and a catalytic subunit, and a variable regulatory subunit. Here we report the crystal structure of the heterotrimeric PP2A holoenzyme involving the regulatory subunit B'/B56/PR61. Surprisingly, the B'/PR61 subunit has a HEAT-like (huntingtin-elongation-A subunit-TOR-like) repeat structure, similar to that of the scaffolding subunit. The regulatory B'/B56/PR61 subunit simultaneously interacts with the catalytic subunit as well as the conserved ridge of the scaffolding subunit. The carboxyterminus of the catalytic subunit recognizes a surface groove at the interface between the B'/B56/PR61 subunit and the scaffolding subunit. Compared to the scaffolding subunit in the PP2A core enzyme, formation of the holoenzyme forces the scaffolding subunit to undergo pronounced conformational rearrangements. This structure reveals significant ramifications for understanding the function and regulation of PP2A.

Amino Acid Sequence↗
PubMed2006

Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins.

The serine/threonine phosphatase protein phosphatase 2A (PP2A) plays an essential role in many aspects of cellular functions and has been shown to be an important tumor suppressor. The core enzyme of PP2A comprises a 65 kDa scaffolding subunit and a 36 kDa catalytic subunit. Here we report the crystal structures of the PP2A core enzyme bound to two of its inhibitors, the tumor-inducing agents okadaic acid and microcystin-LR, at 2.6 and 2.8 A resolution, respectively. The catalytic subunit recognizes one end of the elongated scaffolding subunit by interacting with the conserved ridges of HEAT repeats 11-15. Formation of the core enzyme forces the scaffolding subunit to undergo pronounced structural rearrangement. The scaffolding subunit exhibits considerable conformational flexibility, which is proposed to play an essential role in PP2A function. These structures, together with biochemical analyses, reveal significant insights into PP2A function and serve as a framework for deciphering the diverse roles of PP2A in cellular physiology.

Amino Acid Sequence↗
PubMed2006

Structure and mechanism of the phosphotyrosyl phosphatase activator.

Phosphotyrosyl phosphatase activator (PTPA), also known as PP2A phosphatase activator, is a conserved protein from yeast to human. Here we report the 1.9 A crystal structure of human PTPA, which reveals a previously unreported fold consisting of three subdomains: core, lid, and linker. Structural analysis uncovers a highly conserved surface patch, which borders the three subdomains, and an associated deep pocket located between the core and the linker subdomains. The conserved surface patch and the deep pocket are responsible for binding to PP2A and ATP, respectively. PTPA and PP2A A-C dimer together constitute a composite ATPase. PTPA binding to PP2A results in a dramatic alteration of substrate specificity, with enhanced phosphotyrosine phosphatase activity and decreased phosphoserine phosphatase activity. This function of PTPA strictly depends on the composite ATPase activity. These observations reveal significant insights into the function and mechanism of PTPA and have important ramifications for understanding PP2A function.

Adenosine Triphosphatases↗
PubMed2006

[Diagnosis and surgical management of 209 cases of orbital cavernous hemangioma].

OBJECTIVE: To study the clinical features, preoperative diagnosis and surgical choice of orbital cavernous hemangioma. METHODS: Records of all cavernous hemangioma patients (209 cases) who were seen in Eye Hospital, Zhongshan Ophthalmic Center, Sun Yat-sen University from January 1, 1986 to December 31, 2000 were reviewed. RESULTS: Among 209 cases, 123 patients were females and 86 were males. The left orbit was affected in 123 cases and the right orbit in 86 cases. No case was bilaterally involved. The mean age was 39.2 years old, ranging from 5 to 68 years. A painless, gradually progressive proptosis and visual disturbance were the main clinical signs. Ninety-five percent (199/209) of them could be accurately diagnosed preoperatively based on ultrasound scan and CT/MRI examination. The tumors were removed successfully by the surgical procedure of standard lateral orbitotomy in 36% (75/209) of patients and anterior orbitotomy in 64% cases (134/209). CONCLUSIONS: Nearly all patients with cavernous hemangioma could be correctly diagnosed by preoperative image studying. The simple surgical procedure of anterior orbitotomy can be successfully used in about two third of cases with less surgical complication.

Adolescent↗
PubMed2006

[Preparation and identification of polyclonal antiserum against heat shock protein 72].

OBJECTIVE: To express fusion protein of histamine (His) and human heat shock protein 72 (hHSP72) in Escherichia coli (E. coli), and to prepare hHSP72 antiserum in rabbit. METHODS: hHSP72 gene was inserted into pPROEX-1. The recombinant vector was identified by restriction endonuclease digestion analysis and sequence. Fusion protein His-hHSP72 was expressed in E. coli under isopropyl-beta-D-thiogalactoside (IPTG) induction. The rabbit antibody against His-hHSP72 was prepared by using purified His-hHSP72 protein as immunogen, and the specificity and sensitivity of polyclonal antibody were identified by Western blot. RESULTS: The restriction endonuclease digestion analysis of recombinant plasmid and sequence demonstrated that the hHSP72 gene had been exactly inserted into pPROEX-1. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed that the relative molecular mass of the fusion protein was about 73 ku. Western blot result proved that the rabbit polyclonal antiserum could fuse with over 20 ng hHSP72 protein when diluted to 1:100,000. CONCLUSION: The polyclonal antibody against hHSP72 can be prepared in E. coli, it is a new reagent with high specificity and sensitivity for the research of hHSP72.

Animals↗
PubMed2005

Migration of intraocular silicone into the cerebral ventricles.

PURPOSE: To report a case in which silicone oil in the eye migrated into the cerebral ventricles and the subarachnoid space. DESIGN: Observational case report. METHODS: A 62-year-old woman presented with proliferative diabetic retinopathy and tractive retinal detachment in her left eye. Par plana vitrectomy and injection of 5,000-centistoke-viscosity silicone oil were performed. Intraocular pressure was elevated after the operation and poorly controlled for 4 months. Eight months after the first operation, the patient felt dizzy. Computed tomography (CT), magnetic resonance imaging (MRI), and optical coherence tomography (OCT) scanning were performed. RESULTS: The CT imaging, MRI, and OCT showed silicone oils migrated into the sella cistena superioris and the cerebral ventricles. Follow-up examination was continued. CONCLUSION: Although silicone oil migrating into the ventricles is unusual, we suggest that every patient undergoing silicone oil tamponade with poorly controlled high intraocular pressure and optic disk atrophy should be carefully evaluated.

Brain Diseases↗
PubMed2005

[Therapeutic efficacy of pralidoxime chloride on acute dichlorvos poisoning].

OBJECTIVE: To study the therapeutic efficacy and mechanism of oxime drug, pralidoxime chloride (PAM-Cl), on acute dichlorvos (DDV) poisoning. METHODS: The toxic signs and survival rate were recorded and ChE activity in blood was determined in treatment group with PAM-Cl and non-treatment group after DDV was given to rats and mice by gastrogavage; the therapeutic efficacy and reactivation of DDV-inhibited ChE by PAM-Cl were observed on the patients with acute DDV poisoning. RESULTS: (1) The alleviated and delayed toxic signs as well as higher survival rate were found in PAM-Cl treatment group compared with non-treatment group. (2) After the rats were exposed to DDV, the ChE activities of whole blood in different time within 24 h were statistically significantly higher in PAM-Cl treatment group than in non-treatment group (P < 0.05). (3) After PAM-Cl treatment, muscular fasciculation and other nicotinic signs in poisoned patients were disappeared and the inhibited blood ChE activities were gradually reactivated to normal level. CONCLUSION: PAM-Cl has therapeutic efficacy against acute toxicity of DDV through its reactivation of inhibited ChE.

Acute Disease↗
PubMed2005

[Therapeutic efficacy of N6-cyclopentyladenosine against acute dichlorvos poisoning].

OBJECTIVE: To study the therapeutic efficacy and mechanism of adenosine receptor agonist N(6)-cyclopentyladenosine (CPA) against acute dichlorvos poisoning. METHODS: Soon after a certain doses of dichlorvos were given to mice and rats by gastrogavage, physiological saline, CPA, atropine or pralidoxime chloride were administered to different groups. Toxic signs and survival rate were recorded and cholinesterase (ChE) activities and acetylcholine (ACh) concentrations in whole blood were determined in treatment group with CPA and non-treatment group after dichlorvos was given to rats by gastrogavage. RESULTS: (1) The alleviated and delayed appearance of toxic signs as well as obvious prolongation of survival time was observed in CPA treatment group compared with non-treatment group. (2) ChE activities in both treatment group with CPA [(0.49 +/- 0.05) U/ml] and non-treatment group [(0.52 +/- 0.04) U/ml] were significantly lower than that [(1.56 +/- 0.15) U/ml] of the control group (P < 0.01), but there was no significant difference between treatment group and non-treatment group (P > 0.05). (3) ACh concentration [(204.24 +/- 20.48) microg/ml] in whole blood of treatment group with CPA was significantly lower than that [(230.91 +/- 25.61) microg/ml] of non-treatment group (P < 0.05). CONCLUSION: CPA has therapeutic efficacy against acute dichlorvos poisoning, which is probably through the decrease in ACh concentration.

Acetylcholine↗
PubMed2005

Effect of erythromycin on gastric dysmotility and neuroendocrine peptides in rats with diabetes mellitus.

OBJECTIVE: To investigate the effect of erythromycin on the contractive activity of the isolated gastric antrum smooth muscle and somatostatin (SS), vasoactive intestinal peptide (VIP), motilin (MTL), and substance P (SP) in plasma and isolated gastric antrum tissue of diabetes mellitus (DM) rat models. METHODS: Thirty male Sprague-Dawley rats were divided into three groups: control group (n = 10), DM group (n = 10), and erythromycin group (DM models with erythromycin treatment, n = 10). A single dose of streptozotocin (100 mg/kg, dissolved in 0.1 mol/L citric acid buffer, pH4.5) was injected intraperitoneally. After 48 to 72 hours, rats with blood glucose above 16.7 mmol/L and urine glucose level to be (+++) to (++++) over one week were considered successful DM models. The resting tension, mean contractile amplitude and frequency of spontaneous change in isolated longitudinal and circular gastric antrum smooth muscle strips were measured. SS, VIP, MTL, and SP levels in plasma and gastric antrum tissue were measured using radioimmunoassay. RESULTS: (1) In the isolated gastric antrum smooth muscle strips, the gastric motility parameters were lower in DM group than those in control group except circular smooth muscle contractile amplitude and longitudinal smooth muscle contractile frequency. The gastric motility parameters were significantly strengthened in erythromycin group, compared with DM group except longitudinal smooth muscle resting tension (P < 0.01). (2) Plasma SS, VIP, and MTL concentrations in DM group were higher than those in control (P < 0.05), while the SP level decreased (P < 0.05). In the gastric antrum, SS of DM group was significantly higher than that of control group (P < 0.01), while SP and MTL levels were lower than those of control group (P < 0.05 and P < 0.01, respectively). However, the level of VIP in gastric antrum tissue did not change among three groups. The plasma level of SS in erythromycin group was higher than that of DM group (P < 0.05). (3) The blood glucose was lower in erythromycin group than DM group (P < 0.01). CONCLUSIONS: Erythromycin has direct effects on contractive activity of gastric smooth muscle in diabetic rats, but there are few effects on neuroendocrine peptides. Gastric-motility disorders in diabetic rats have a correlation with the changes of neuroendocrine peptide levels in plasma and gastric antrum tissue.

Animals↗
PubMed2005

[Clinical observation on acupuncture at pain point combined with moxibustion at Zusanli (ST 36) for treatment of periarthritis of shoulder].

OBJECTIVE: To find an effective therapy for periarthritis of shoulder. METHODS: Sixty cases were divided into two groups, 30 cases in each group. They were treated by acupuncture at pain point combined with moxibustion at Zusanli (ST 36) and routine acupuncture, respectively. Pain of the shoulder and movement functions of shoulder joints were used as indexes of therapeutic effects and their therapeutic effects were compared. RESULTS: The total effective rate was 96.7% in the treatment group and 90.0% in the routine group with no significant difference between the two groups (P > 0.05); the cured rate in the two groups were 46.7% and 20.0% respectively with a significant difference between the two groups (P < 0.05). There were statistically significant differences between the two groups in improvement of movement function of shoulder joints and alleviation of pain (both P < 0.01). CONCLUSION: Acupuncture at pain points combined with moxibustion at Zusanli (ST 36) in increase of the cured rate and alleviation of pain, and improvement of movement function of shoulder joints is better than the routine acupuncture and moxibustion for treatment of periarthritis of shoulder.

Acupuncture Therapy↗
PubMed2003

[Redox-dependent changes in structure and function of hHSF1].

To evaluate the effects of cysteine-SH-directed regents on the redox status, structure and function of human heat shock transcription factor 1 (hHSF1), treatment in vitro of hHSF1 with 0.3 0.5 mmol/L oxidizing reagent diamide (DM) and treatment in vivo of HeLa cells with 1 mmol/L buthionine sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase, promoted the formation of a compact, intramolecularly disulfide-crosslinked, stable monomeric form of ox-hHSF1, and blocked the trimerization and activation of HSF1. The effects of diamine were dose-dependent and readily could be completely reversed by adding 0.4 0.5 mmol/L reducing reagent dithiothreitol (DTT) to the samples prior to gel electrophoresis. Computer modeling of the alpha-helical coiled-coil domains of the HSF1 monomer and trimer showed that the alignment of the N- and C-terminal hydrophobic repeats of HSF1 monomer could bring C(3)(Cys(153))close to C(4) and C(5)(Cys(373) and Cys(378), respectively), in positions permissible for disulfide bond formation under appropriate experimental conditions. The results suggest that redox-dependent thiol-disulfide exchange can provide a mechanism for regulation the conformation and activity of hHSF1.

Buthionine Sulfoximine↗
PubMed2003

[The inhibition effect of interleukin-1 receptor antagonist on interleukin-1 alpha-induced intercellular adhesion molecule-1 expression on orbital fibroblasts and adhesion of peripheral blood mononuclear cells].

OBJECTIVE: The aim was to identify whether interleukin-1 receptor antagonist (IL-1ra) inhibits interleukin-1 alpha (IL-1 alpha)-induced intercellular adhesion molecule-1 (ICAM-1) expression on cultured orbital fibroblasts, and adhesion of peripheral blood mononuclear cells (PBMC) to orbital fibroblasts, and to investigate the clinical application potential of IL-1ra in the treatment of Graves' ophthalmopathy (GO). METHODS: Cultured orbital fibroblasts from patients with GO and controls were challenged with IL-1 alpha or/and IL-1ra. Immunocytochemical staining was used to examine the changes of ICAM-1 in response to IL-1ra treatment; fluorescent photomicroscope was used to measure the adhesion between the labeled PBMC and orbital fibroblasts. Neutralizing antibody against ICAM-1 was used to demonstrate the role of ICAM-1 in the IL-1 alpha-induced adhesion. RESULTS: IL-1ra inhibits IL-1 alpha-induced ICAM-1 expression in cultured orbital fibroblasts both from GO patients and controls; IL-1ra inhibits IL-1 alpha-induced adhesion of PBMC to orbital fibroblasts in a concentration and time dependent manner. Moreover, a monoclonal anti-human ICAM-1 antibody produced a concentration dependent inhibition of the IL-1 alpha-induced adhesion of PBMC to the fibroblasts. CONCLUSIONS: IL-1ra inhibits IL-1 alpha-induced ICAM-1 expression in cultured orbital fibroblasts and the adhesion of PBMC to fibroblasts. IL-1 alpha-induced ICAM-1 expression may play an important role in the adhesion process. IL-1ra may be useful in the prevention or treatment of GO.

Cell Adhesion↗
PubMed2003

[The expression of 5 immune molecules on rat peripheral leucocytes after heart transplantation].

AIM: To observe 5 kinds of immune molecule expressions on rat peripheral leucocytes at varying time points after ectopic heart transplantation and explore the mechanism of acute rejection reaction. METHODS: Donor's heart derived from SD rat was transplanted into the abdomen cavity of Wistar rat by anastomosis of donor's aorta and pulmonary artery to recipient's abdominal aorta and inferior-venacava for establishing coronary perfusion. Before and after transplantation, peripheral leucocytes were isolated from venous blood and labelled with the monoclonal antibodies(mAbs) against CD4, CD8, IL-2R, ICAM-I and MHC-II molecules, respectively. The these molecule levels were assessed by flowcytometry. Simultaneity, graft's pathological changes and their survival rate were observed. RESULTS: At 24 hours after transplantation, MHC-II molecule expression was increased, while expressions of CD4, IL-2R and ICAM-I were significantly decreased, but CD8 expression had no change. At 72 hours after operation, the expressions of CD4, CD8 and IL-2R increased and expressions of CD8 and IL-2R reached to peak. At 7-10 days after operation, except that CD4 expression increased continuously, the expressions of 4 other molecules decreased gradually. The survival rate of graft at varying times after operation were 100%( 24 h), 85.7%(3 days), 16.7%(7 days) and, 0 (10 and 12 days), respectively. Pathological examination showed that there was no notable pathological change in cardiac muscle tissue. At the third day after operation, 4 out of 7 transplanted hearts had only grade I A pathological change. Grade II and above grade II pathological changes were observed in all 6 grafts at the 7th day after operation. CONCLUSION: These data indicate that graft rejection reaction begin to appear in first 72 hours, and effector phase of the reaction appear mainly within 3-7 days after heart transplantation.

Animals↗
PubMed2002

Redox-dependent regulation of the conformation and function of human heat shock factor 1.

We present here evidence that redox-dependent thiol-disulfide exchange can provide a mechanism regulating the conformation and activity of the human heat shock transcription factor 1 (HSF1). Diamide and dithiothreitol were reagents used respectively to promote and reverse disulfide cross-link, and the resolution and detection of redox conformers of HSF1 were done according to recently published methods [Manalo, D. J., and Liu, A. Y.-C. (2001) J. Biol. Chem. 276, 23554-23561]. We showed that preincubation of the latent HSF1 monomer with diamide inhibited the in vitro heat-induced activation and trimerization of HSF1 and caused the formation of ox-hHSF1, a compact, disulfide cross-linked HSF1 conformer detectable in immuno-Western blot assay. These effects of diamide were dose-dependent and were rapidly and quantitatively reversed by dithiothreitol. Cysteine site-specific mutants of HSF1 were constructed and used to determine which of the five cysteine residues may be engaged in disulfide cross-link. Analysis of the in vitro transcribed and translated HSF1 proteins showed that while mutation of C1 (amino acid 36) and C2 (amino acid 103) had no effect on the redox sensitivity of HSF1, the mutation of C3 (amino acid 153) or double mutation of C4 and C5 (amino acids 373 and 378, respectively) to serine rendered HSF1 insensitive to diamide and prevented its conversion to ox-HSF1. HSF1 with a single cysteine to serine mutation at either the C4 or C5 position gave different ox-HSF1 conformers in the presence of diamide, suggesting that C3 could be disulfide cross-linked to either C4 or C5. The possibility that HSF1 may have integrated redox chemistry of cysteine sulfhydryl into its functional response in higher mammalian cells is discussed.

Base Sequence↗
PubMed2002

Chlorinated and polycyclic aromatic hydrocarbons in riverine and estuarine sediments from Pearl River Delta, China.

Spatial distribution of chlorinated hydrocarbons [chlorinated pesticides (CPs) and polychlorinated biphenyls (PCBs)] and polycyclic aromatic hydrocarbons (PAHs) was measured in riverine and estuarine sediment samples from Pearl River Delta, China, collected in 1997. Concentrations of CPs of the riverine sediment samples range from 12 to 158 ng/g, dry weight, while those of PCBs range from 11 to 486 ng/g. The CPs concentrations of the estuarine sediment samples are in the range 6-1658 ng/g, while concentrations of PCBs are in the range 10-339 ng/g. Total PAH concentration ranges from 1168 to 21,329 ng/g in the riverine sediment samples, whereas the PAH concentration ranges from 323 to 14,812 ng/g in the sediment samples of the Estuary. Sediment samples of the Zhujiang River and Macao harbor around the Estuary show the highest concentrations of CPs, PCBs, and PAHs. Possible factors affecting the distribution patterns are also discussed based on the usage history of the chemicals, hydrologic condition, and land erosion due to urbanization processes. The composition of PAHs is investigated and used to assess petrogenic, combustion and naturally derived PAHs of the sediment samples of the Pearl River Delta. In addition, the concentrations of a number of organic compounds of the Pearl River Delta samples indicate that sediments of the Zhujiang river and Macao harbor are most likely to pose biological impairment.

Carbon↗
PubMed2002

[The distribution of serum homocysteine and its associated factors in a population of 1 168 subjects in Beijing area].

OBJECTIVE: To describe serum homocysteine distribution and its associated factors in population of urban and rural areas in Beijing. METHODS: The study population was represented by a randomly selected sample with 1 168 subjects, including both males and females aged 35 - 64. The levels of serum homocycteine were compared and the correlation with other risk factors were analyzed statistically. RESULTS: (1) Geometric mean of serum homocycteine was 15.4 micromol/L in males and 12.2 micromol/L in females (P < 0.001). (2) There was a significant difference in homocysteine levels between urban population and rural population. Men from rural area had 1.5 times higher homocyteine than from urban (18.0 micromol/L vs 12.0 micromol/L, P < 0.001), while the rural women had 1.3 times higher homocysteine level than urban women did. (3) The prevalence rate of hyperhomocysteinemia was 15.3% in population aged 35 - 64 in Beijing area. (4) Gender, residential location (urban or rural), smoking and education had independent effects on level of serum homocysteine by multivariate analysis. CONCLUSION: Population in Beijing had higher serum level and prevalence rate of homocysteine than some western countries. Gender, geographic distribution, smoking and education had some influence on homocysteine level.

Adult↗
PubMed2002

[The effect of the dosage of TiO2 and its surface-loaded silver on the photocatalytic degradation of aroclor1260].

The dosage of TiO2 and its surface-loaded silver had notable effect on the photocatalytic degradation of Aroclor1260, under ultraviolet light. The dosage of TiO2 had no proportion to the degradation rate of Aroclor1260, but had an optimal value, which was 3 g/L under the experimental condition. The degradation rate of Aroclor1260 increased with the increasing of loading silver, and the PCBs congeners with higher concentration had higher degradation rate. The catalytic activity of TiO2 increased with the amount of loading silver increasing.

Aroclors↗