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Biomedical subjects

J Tan

Publications and source records attributed to J Tan.

At least 91 records · Page 5Linked to original sources
PubMed2000

Conserved regions in the Epstein-Barr virus leader protein define distinct domains required for nuclear localization and transcriptional cooperation with EBNA2.

Epstein-Barr virus (EBV) EBNA-LP is a latent protein whose function is not fully understood. Recent studies have shown that EBNA-LP may be an important EBNA2 cofactor by enhancing EBNA2 stimulation of the latency C and LMP-1 promoters. To further our understanding of EBNA-LP function, we have introduced a series of mutations into evolutionarily conserved regions and tested the mutant proteins for the ability to enhance EBNA2 stimulation of the latency C and LMP-1 promoters. Three conserved regions (CR1 to CR3) are located in the repeat domains that are essential for the EBNA2 cooperativity function. In addition, three serine residues are also well conserved in the repeat domains. Clustered alanine mutations were introduced into CR1 to CR3, and the conserved serines were also changed to alanine residues in an EBNA-LP with two repeats, which is the minimal protein able to cooperate with EBNA2. Mutations introduced into CR1a had no effect on EBNA-LP function, while mutations introduced into CR1b resulted in EBNA-LP with slightly decreased activity. Mutations in CR1c and CR2 resulted in proteins that no longer localized exclusively to the nucleus and also had no EBNA2 cooperation activity. Mutations introduced into conserved serines S5/71 resulted in proteins with slightly higher activity, while mutations introduced into conserved serines S35/101 or in CR3 (which contains S60/126) resulted in EBNA-LP proteins with substantially reduced activity. The potential karyophilic signals within EBNA-LP CR1c and CR2 were also examined by introducing oligonucleotides encoding these positively charged amino acid groupings into a cytoplasmic test protein, herpes simplex virus DeltaIE175, and by examining the intracellular localization of the resulting proteins. This assay identified a strong nuclear localization signal between EBNA-LP amino acids 43 and 50 (109 to 117 in the second W repeat) comprising CR2, while EBNA-LP amino acids 29 to 36 (91 to 98 in the second W repeat) were unable to function independently as a nuclear localization signal. However, a combination of amino acids 29 to 50 resulted in more efficient nuclear localization than with amino acids 43 to 50 alone. These results indicate that EBNA-LP has a bipartite nuclear localization signal and that efficient nuclear localization is essential for EBNA2 cooperativity function. Interestingly, EBNA-LP with only a single repeat localized exclusively to the cytoplasm, providing an explanation for why this isoform has no activity. In addition, two conserved serine residues which are distinct from nuclear import functions are important for EBNA2 cooperativity function.

Amino Acid Sequence↗
PubMed2000

Acute posterior vitreous detachment: the predictive value of vitreous pigment and symptomatology.

AIM: To establish whether the presence of a retinal break can be predicted either by the presence of a positive Shafer's sign (pigment granules in the anterior vitreous) or symptomatology in patients presenting with an acute posterior vitreous detachment (PVD). METHODS: 200 eyes of 200 phakic patients with a symptomatic PVD of less than 1 month's duration underwent documentation of symptomatology and examination of the anterior vitreous for the presence of pigment granules. Indentation ophthalmoscopy was then carried out by an experienced vitreoretinal surgeon with no knowledge of the symptomatology or anterior vitreous gel examination findings. A second prospective group of 115 consecutive patients were assessed in a similar manner before primary rhegmatogenous retinal detachment repair. RESULTS: In 200 eyes presenting with an acute PVD, 25 were found to have an associated retinal break, 23 of which were also Shafer positive. In 115 eyes presenting for retinal detachment repair, 111 had an associated PVD and were found to be Shafer positive. Symptomatology was not predictive of an associated retinal break in the PVD group or in those presenting with a retinal detachment. CONCLUSION: The increased use of Shafer's sign is recommended as a valuable aid in determining which patients require urgent referral for an expert retinal examination. It is not possible to predict those patients with a retinal break secondary to PVD on the basis of symptomatology alone.

Acute Disease↗
PubMed2000

Protein inhibitor of activated STAT-1 (signal transducer and activator of transcription-1) is a nuclear receptor coregulator expressed in human testis.

An androgen receptor (AR) interacting protein was isolated from a HeLa cell cDNA library by two-hybrid screening in yeast using the AR DNA+ligand binding domains as bait. The protein has sequence identity with human protein inhibitor of activated signal transducer and activator of transcription (PIAS1) and human Gu RNA helicase II binding protein (GBP). Binding of PIAS1 to human AR DNA+ligand binding domains was androgen dependent in the yeast liquid beta-galactosidase assay. Activation of binding by dihydrotestosterone was greater than testosterone > estradiol > progesterone. PIAS1 binding to full-length human AR in a reversed yeast two hybrid system was also androgen dependent. [35S] PIAS1 bound a glutathione S-transferase-AR-DNA binding domain (amino acids 544-634) fusion protein in affinity matrix assays. In transient cotransfection assays using CV1 cells with full-length human AR and a mouse mammary tumor virus luciferase reporter vector, there was an androgen-dependent 3- to 5-fold greater increase in luciferase activity with PIAS1 over that obtained with an equal amount of control antisense cDNA or mutant PIAS1. Constitutive transcriptional activity of the AR N-terminal+DNA binding domain was increased 6-fold by PIAS1. PIAS1 also enhanced glucocorticoid receptor transactivation in response to dexamethasone but inhibited progesterone-induced progesterone receptor transactivation in the same assay system. mRNA for PIAS1 was highly expressed in testis of human, monkey, rat, and mouse. In rat testis the onset of PIAS1 mRNA expression coincided with the initiation of spermatogenesis between 25-30 days of age. Immunostaining of human and mouse testis with PIAS1-specific antiserum demonstrated coexpression of PIAS1 with AR in Sertoli cells and Leydig cells. In addition, PIAS1 was expressed in spermatogenic cells. The results suggest that PIAS1 functions in testis as a nuclear receptor transcriptional coregulator and may have a role in AR initiation and maintenance of spermatogenesis.

Aged↗
PubMed2000

[The application of meshed acellular dermis xenograft (pigskin) with split thickness skin autograft in 23 patients].

OBJECTIVE: An effective and inexpensive coverage, which can prevent scar formation and fill up scar tissue depression for full thickness skin burns in 23 patients was presented. METHODS: A deepithelized and acellular basement membranes of dermis from freshly harvested pigskin was obtained as meshed acellular dermis xenograft. The patients were treated in one or two stages. Two stages, 7 day postoperative the meshed acellular xenograft, a split thickness skin autograft was applied. One stage, the meshed acellular xenograft and split thickness skin autograft were applied at same time. RESULTS: The take rate of two staged treatment was (87.0 +/- 25.4)% and one stage was (60.3 +/- 3.4)%. All grafts showed in pink or near normal skin color and felt soft and smooth. CONCLUSIONS: The combination of meshed acellular dermis xenograft and split thickness skin autograft demonstrated an ideal way for the coverage of full thickness skin burn, which is effective and inexpensive.

Adolescent↗
PubMed2000

[Experimental study of shuangcao granule no. 1 on duck hepatitis B virus in ducklings].

OBJECTIVE: To study the in vivo anti-viral effect of a Chinese drug, composite Shuangcao Anti-Jaundice Granule No. 1(SCG-1), on duck hepatitis B virus (DHBV). METHODS: Guangzhou brown spot ducklings infected with DHBV were used as the hepatitis B animal model, for which, 1-day old ducklings were infected with DHBV. Positive DHBV-DNA in ducklings sera were detected 13 days after the infection, and then SCG-1 was given for 14 days and DHBV-DNA was detected by dot-blot hybridization test. RESULTS: After medicated with SCG-1 [10 g/(kg.day) and 5 g/(kg.day)] 7 days and 14 days, optic density value (OD value) of DHBV-DNA in ducklings' sera were obviously lower than that before treatment, there was significant difference. But rebound phenomenon appeared in both groups 3 days after stopping medication (P < 0.05). CONCLUSION: SCG-1 could inhibit the replication of DHBV-DNA in Guangzhou ducklings.

Animals↗
PubMed2000

[Comparison of HLA class I typing by serology with DNA typing].

OBJECTIVE: To compare HLA class I typing by serology with PCR-SSP method in the Chinese population. METHODS: HLA-A and -B antigens were typed by serology with microlymphocytotoxicity and DNA typing with PCR-SSP in 525 clinical samples. Reliability, reproducibility and clinical practicability of both methods were compared according to the typing results. RESULTS: Serological typing for HLA class I was rapid and simple, costing 3 hours. The discrepancy rate between serology and PCR-SSP for HLA-A antigen was 9.0%, consisting of 21 antigens being incorrectly interpreted by serology and 26 of serological "blanks" turning out to be definable alleles by DNA typing. The discrepancy rate for HLA-B antigen was 12.2%, containing 39 antigens being incorrectly interpreted and 35 of serological "blanks" turning out to be definable alleles by PCR-SSP typing. DNA typing for HLA class I by PCR-SSP proved to be an accurate, reliable and well-reproducible technique within 5 hours. While it was difficult to suit clinical assay by a large scale screening because of complicated operation and high technical condition. CONCLUSION: DNA typing for HLA class I by PCR-SSP is suitable for clinical application in the Chinese population with a higher precision than serology. Screening test by serology is recommended. Ambiguous or blank antigens by serology should be retyped by DNA typing.

Adolescent↗
PubMed2000

[HLA-amino acid residue matching in organ transplantation].

OBJECTIVE: To present a new matching policy-HLA amino acid residue matching (Res M) for Chinese population. METHODS: Based on the outcome of genotyping for HLA alleles in massive samples, we presented new Res M according to 10 groups of amino acid residue for class I and, groups of DR/DQ for class II and compared them with HLA six-antigen match program (Ag M). The influence of Res M on early renal function, acute rejection and 1-5 year graft survivals were retrospectively analyzed in 316 cases of first cadaver kidney transplantation. RESULTS: The rate of Res-matched transplants increased greatly. The rate of 0 mismatch (MM) recipients increased from 0.3% by Ag M to 10% by Res M, and that of 0-1 MM transplants from 3.2% to 42.4%. Clinical study showed that 1 - 5 year graft survival with 0 - 1 Res-MM was similar to kidneys with 0 - 2 Ag-MM. Compared to 3 - 4 Res-MM, the early renal function obviously improved (88.8% vs 46.7%), acute rejection decreased (14.9% vs 86.9%), 1 - 5 year survival was increased by 10% - 26% (P < 0.05), and graft survival increased by 14% - 35% (P < 0.01) in recipients with 0 - 1 Res-MM. Cox regression showed that in 10 factors affecting the graft survival, Res-MM was most significant (risk ratio 21.73). CONCLUSION: New Res M has proved to be suitable for clinical application in Chinese population, especially for cadaver kidney transplantation.

Graft Rejection↗
PubMed2000

[Analysis on the intervention effect of HIV/AIDS cases].

OBJECTIVE: To study the effect of a comprehensive intervention strategy on the HIV infected individuals and their families. METHODS: Eleven HIV positive persons and their families were included to a comprehensive intervention strategy including routine surveillance, safer sex education and improving the status of hygiene. The outcome was compared with 2 fully developed AIDS cases who were not included to the intervention strategy. RESULTS: Of those HIV positive persons, that subjected to the intervention strategy, none had developed to AIDS, with only 1 transmitted HIV to his spouse among the 6 married individuals. All of their families were stable. Of those that not had been subjected, 2 individuals developed to AIDS and transmission in family was confirmed. CONCLUSION: The comprehensive intervention strategy on HIV/AIDS was effective which could the possibility of HIV in-family transmission and enhance the quality of life and the stability of their families.

Acquired Immunodeficiency Syndrome↗
PubMed2000

[Effects of Nilestriol on reproductive system in ovariectomized rats].

The purpose of this study was to determine the effects of Nilestriol on reproductive system. Female SD rats, aged 4 months, were randomly divided into three groups. The OVX group's rats were subjected to bilateral ovariectomy, the SHAM group's rats received sham surgery; the Nilestriol(CEE3) group's rats were subjected to bilateral ovariectomy and treated with CEE3(0.15 mg/100 g BW, once a week). A computerized image analyzer was used to evaluate the endometrial pathological changes 10 weeks later. The weight of uterus was measured. The results showed that in OVX group, atrophic uteri; and atrophied endometria were noted. The weight of uterus was increased in CEE3 group, compared with that in OVX group (642.20 +/- 283.60 mg vs. 297.00 +/- 106.90 mg, P < 0.05). The volume fraction of endometrial glands was also significantly elevated in CEE3 group, compared with that in OVX group (1.84% vs 0.58%). The endometria in CEE3 group were at an early proliferative stage. These suggest that Nilestriol has a slight stimulating effect on the uteri of ovariectomized rats, including their endometria and uterine smooth muscles. Nilestriol is suited to be used in combination with progestogen.

Animals↗
PubMed1999

Microglial activation resulting from CD40-CD40L interaction after beta-amyloid stimulation.

Alzheimer's disease (AD) has a substantial inflammatory component, and activated microglia may play a central role in neuronal degeneration. CD40 expression was increased on cultured microglia treated with freshly solublized amyloid-beta (Abeta, 500 nanomolar) and on microglia from a transgenic murine model of AD (Tg APPsw). Increased tumor necrosis factor alpha production and induction of neuronal injury occurred when Abeta-stimulated microglia were treated with CD40 ligand (CD40L). Microglia from Tg APPsw mice deficient for CD40L demonstrated reduction in activation, suggesting that the CD40-CD40L interaction is necessary for Abeta-induced microglial activation. Finally, abnormal tau phosphorylation was reduced in Tg APPsw animals deficient for CD40L, suggesting that the CD40-CD40L interaction is an early event in AD pathogenesis.

Alzheimer Disease↗
PubMed1999

Ligation of microglial CD40 results in p44/42 mitogen-activated protein kinase-dependent TNF-alpha production that is opposed by TGF-beta 1 and IL-10.

Recently, it has been demonstrated that the CD40 receptor is constitutively expressed on cultured microglia at low levels. Ligation of CD40 by CD40 ligand on these cells results in microglial activation, as measured by TNF-alpha production and neuronal injury. However, the intracellular events mediating this effect have yet to be investigated. We report that ligation of microglial CD40 triggers activation of p44/42 mitogen-activated protein kinase (MAPK). This effect is evident 30 min posttreatment, and progressively declines thereafter (from 30 to 240 min). Phosphorylated p38 MAPK is not observed in response to ligation of microglial CD40 across the time course examined. Inhibition of the upstream activator of p44/42 MAPK, mitogen-activated protein/extracellular signal-related kinase kinase 1/2, with PD98059, decreases phosphorylation of p44/42 MAPK and significantly reduces TNF-alpha release following ligation of microglial CD40. Furthermore, cotreatment of microglial cells with CD40 ligand and TGF-beta1 or IL-10, or both, inhibits CD40-mediated activation of p44/42 MAPK and production of TNF-alpha in a statistically interactive manner. Taken together, these data show that ligation of microglial CD40 triggers TNF-alpha release through the p44/42 MAPK pathway, an effect that can be opposed by TGF-beta1 and IL-10.

Animals↗
PubMed1999

Alzheimers disease is not associated with the hypertension genetic risk factors PLA(2) or G protein beta3, either independently or interactively with apolipoprotein E.

Growing evidence suggests that hypertension and Alzheimers disease (AD) may share a common etiology. To evaluate the contribution to AD of genetic factors associated with hypertension, we genotyped clinic and community-based AD cases and controls for polymorphisms within the pancreatic PLA(2) gene and the G protein beta3 subunit gene, both of which are located on chromosome 12. Our results do not support an independent association between either of these genes and AD. We further assessed the possibility that either of these genes may interact with the apolipoprotein E gene, a known risk factor for hypertension and AD, on predicting AD. We were unable to find statistical interaction between either the pancreatic PLA(2) or Gbeta3 genes and the apolipoprotein E gene on risk for AD. These results do not support a shared genetic etiology between hypertension and AD. Possibly, a clinical association between these diseases could be due to pathophysiologic interactions.

Aged↗
PubMed1999

Smoking in China: findings of the 1996 National Prevalence Survey.

CONTEXT: As the world's largest producer and consumer of tobacco products, China bears a large proportion of the global burden of smoking-related disease and may be experiencing a tobacco epidemic. OBJECTIVE: To develop an evidence-based approach supporting tobacco control initiatives in China. DESIGN AND SETTING: A population-based survey consisting of a 52-item questionnaire that included information on demographics, smoking history, smoking-related knowledge and attitudes, cessation, passive smoke exposure, and health status was administered in 145 disease surveillance points in the 30 provinces of China from March through July 1996. PARTICIPANTS: A nationally representative random sample of 128766 persons aged 15 to 69 years were asked to participate; 120298 (93.8%) provided data and were included in the final analysis. About two thirds of those sampled were from rural areas and one third were from urban areas. MAIN OUTCOME MEASURES: Current smoking patterns and attitudes; changes in smoking patterns and attitudes compared with results of a previous national survey conducted in 1984. RESULTS: A total of 41187 respondents smoked at least 1 cigarette per day, accounting for 34.1% of the total number of respondents, an increase of 3.4 percentage points since 1984. Current smoking continues to be prevalent among more men (63%) than women (3.8%). Age at smoking initiation declined by about 3 years for both men and women (from 28 to 25 years). Only a minority of smokers recognized that lung cancer (36%) and heart disease (4%) can be caused by smoking. Of the nonsmokers, 53.5% were exposed to environmental tobacco smoke at least 15 minutes per day on more than 1 day per week. Respondents were generally supportive of tobacco control measures. CONCLUSION: The high rates of smoking in men found in this study signal an urgent need for smoking prevention and cessation efforts; tobacco control initiatives are needed to maintain or decrease the currently low smoking prevalence in women.

Adolescent↗
PubMed1999

Influence of synthetic polymers on neutrophil migration in three-dimensional collagen gels.

In vitro studies of cell migration within three-dimensional polymeric materials are essential for understanding cell behavior and for developing new biomedical materials. Human neutrophil motility was examined in hydrated collagen gels containing various synthetic polymers. Physical mixtures of collagen and certain water-soluble polymers formed stable gels that were good substrates for cell migration. Addition of either polyethylene glycol (PEG) or the pluronictrade mark copolymer F68 did not change the morphological or mechanical properties of collagen gels, as determined by SEM and oscillatory rheometry; however, addition of either polymer significantly inhibited cell motility in both a modified 96-well chemotaxis chamber assay and a direct visual assay. Although the mechanism for this observed polymer inhibition of neutrophil migration is not yet clear, these results suggest that PEG and F68, two widely used biomedical polymers that are considered to be relatively "inert," may cause significant inhibition of cell motility.

Adult↗
PubMed1999

Induction of CD40 on human endothelial cells by Alzheimer's beta-amyloid peptides.

Growing evidence suggests that beta-amyloid (Abeta) peptides play a central role in mediating vascular endothelium dysfunction, but the extent to which immune mechanisms are involved in this process remains unclear. To explore such mechanisms, we incubated cultured human aortic endothelial cells (HAEC) with freshly solublized Abeta and examined expression of a central immunoregulatory molecule, CD40, in these cells using reverse transcriptase-polymerase chain reaction, Western immunoblotting, and Flow cytometry. Our results show that treatment of endothelial cells with Abeta1-40, Abeta1-42 or gamma interferon (IFN-gamma) results in a dose-dependent induction of endothelial CD40 expression. Furthermore, ligation of endothelial CD40 and simultaneous treatment of human endothelial cells with IFN-gamma or Abeta peptides leads to a significant release of interleukin-1beta (IL-1beta), a marker for endothelial cell activation. Since IL-1beta is an important inflammatory response mediator, these findings suggest that the functional role of Abeta-induced endothelial CD40 may be promotion of the inflammatory cascade in vascular endothelial cells.

Alzheimer Disease↗
PubMed1999

Bcl-X(L) inhibits apoptosis and necrosis produced by Alzheimer's beta-amyloid1-40 peptide in PC12 cells.

Recent studies have shown that neuronal apoptosis induced by the Alzheimer's disease (AD) beta-amyloid peptide (Abeta) is related to alteration of the Bax/Bcl-2 ratio. It has been demonstrated that Bcl-X(L) (Bcl-X(L) = protein, bcl-X(L) = gene), a Bcl-2-related protein, prevents apoptosis in mammalian cells. Additionally, TGF-beta1 is able to protect cultured neuronal cells from Abeta-induced apoptosis via upregulation of bcl-X(L) and bcl-2 gene expression. We show that Abeta treatment (500 nM, freshly solubilized) results in apoptosis and necrosis in differentiated PC12 cells maintained with a low dose of NGF-beta (1 ng/ml). To investigate whether transfection of PC12 cells with bcl-X(L) could block Abeta-induced apoptosis, we transfected these cells with a bcl-X(L) construct (pcDNA-bcl-X(L)). Data show that bcl-X(L) significantly inhibits both early-stage apoptosis and late-stage apoptosis/necrosis produced by Abeta treatment (1000 nM) in pcDNA3-bcl-X(L)-transfected PC12 cells as compared with pcDNA3 vector-transfected PC12 cells. These results suggest that Bcl-X(L) exhibits both anti-necrotic as well as anti-apoptotic roles in Abeta-challenged PC12 cells.

Alzheimer Disease↗
PubMed1999

Activation of microglial cells by the CD40 pathway: relevance to multiple sclerosis.

It is well known that microglial cells perform a key role in mediating inflammatory processes, which are associated with neurodegenerative diseases such as multiple sclerosis (MS). In this study, we report that CD40 expression on microglia is greatly enhanced by a low dose (10 U/ml) of IFN-gamma. We also find that ligation of microglial CD40 by CD40L triggers a significant production of TNF-alpha. Activation of microglia by ligation of CD40 in the presence of IFN-gamma results in cultured cortical neuronal injury, which is markedly attenuated by blockade of the CD40 pathway or neutralization of TNF-alpha. Finally, we find significant levels of IFN-gamma and TNF-alpha in the medium of co-cultured activated CD4+ T cells and microglial cells, showing that microglia can supply the CD40 receptor to activated CD4+ T cells and suggesting that this cellular interaction is a key event in MS pathophysiology.

Animals↗