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Biomedical subjects

S Tang

Publications and source records attributed to S Tang.

At least 19 recordsLinked to original sources

Prolactin family miniarray: a tool for evaluating uteroplacental-trophoblast endocrine cell phenotypes.

The prolactin family represents a group of hormones and cytokines that participate in the control of maternal and fetal adaptations to pregnancy. The aim of this study was to develop a simple assay for monitoring patterns of prolactin family gene expression in rats and mice. Prolactin family cDNAs were spotted on to nylon membranes. Total RNA was extracted from tissues or cells. cDNAs were generated, radiolabelled using reverse transcriptase, and used as probes to hybridize with the prolactin family miniarrays. Pituitary, uterine decidual tissue and placenta each expressed a unique profile of prolactin family members. Placental tissues exhibited regional- and temporal-specific patterns of expression. Prolactin family gene expression differed markedly in mid-pregnant versus late gestation placental tissues and between the junctional and labyrinthine zones of the chorioallantoic placenta. Marked changes in prolactin family gene expression were also observed in cultured trophoblast cells undergoing differentiation. In conclusion, the prolactin family miniarray assay is an effective method for evaluating the endocrine phenotype of the uterus, placenta and trophoblast cells.

Animals↗

Choice behavior of Drosophila facing contradictory visual cues.

We studied the underlying neural mechanism of a simple choice behavior between competing alternatives in Drosophila. In a flight simulator, individual flies were conditioned to choose one of two flight paths in response to color and shape cues; after the training, they were tested with contradictory cues. Wild-type flies made a discrete choice that switched from one alternative to the other as the relative salience of color and shape cues gradually changed, but this ability was greatly diminished in mutant (mbm1) flies with miniature mushroom bodies or with hydroxyurea ablation of mushroom bodies. Thus, Drosophila genetics may be useful for elucidating the neural basis of choice behavior.

Animals↗

Non-specific deadenylation and deguanylation of naked RNA catalyzed by ricin under acidic condition.

Ricin A-chain catalyzes the hydrolysis of the N-glycosidic bond of a conserved adenosine residue at position 4324 in the sarcin/ricin domain of 28S RNA of rat ribosome. The GAGA tetraloop closed by C-G pairs is required for recognition of the cleavage site on 28S ribosomal RNA by ricin A-chain. In this study, ricin A-chain (reduced ricin) exhibits specific depurination on a synthetic oligoribonucleotide (named SRD RNA) mimic of the sarcin/ricin domain of rat 28S ribosomal RNA under neutral and weak acidic conditions. Furthermore, the activity of intact ricin is also similar to that of ricin A-chain. However, under more acidic conditions, both enzymes lose their site specificity. The alteration in specificity of depurination is not dependent on the GAGA tetraloop of SRD RNA. A higher concentration of KCl inhibits the non-specific N-glycosidase activity much more than the specific activity of ricin A-chain. In addition, characterization of depurination sites by RNA sequencing reveals that under acidic conditions ricin A-chain can release not only adenines, but also guanines from SRD RNA or 5S ribosomal RNA. This is the first report of the non-specific deadenylation and deguanylation activity of ricin A-chain to the naked RNA under acidic conditions.

Adenosine Monophosphate↗

Chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma in combination with highly active antiretroviral therapy.

PURPOSE: This study investigated the efficacy, toxicity, and pharmacokinetic interactions resulting from simultaneous combination chemotherapy and highly active antiretroviral therapy (HAART) for patients with human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL). In addition, the effects on viral load, CD4 counts, and opportunistic infections were examined with the use of combination chemotherapy combined with HAART. PATIENTS AND METHODS: Sixty-five patients with previously untreated and measurable disease at any stage of HIV-associated NHL of intermediate or high grade were entered onto this study at 17 different centers. The first 40 patients entered onto the study received reduced doses of cyclophosphamide and doxorubicin, combined with vincristine and prednisone (modified CHOP [mCHOP]), whereas the subsequent 25 patients entered onto the study received full doses of CHOP combined with granulocyte colony-stimulating factor (G-CSF). All patients also received stavudine, lamivudine, and indinavir. RESULTS: The complete response rates were 30% and 48% among patients who received mCHOP and full-dose CHOP combined with HAART, respectively. Grade 3 or 4 neutropenia occurred in 25% of patients receiving mCHOP and 12% of those receiving full-dose CHOP combined with G-CSF (25% v 12%). There were similar numbers of patients with grade 3 or 4 hyperbilirubinemia (12% and 17%), constipation and abdominal pain (18% and 17%), and transaminase elevation (48% and 52%) on the modified and full-dose arms of the study, respectively. Doxorubicin clearance and indinavir concentration curves were similar among patients on this study and historical controls, whereas cyclophosphamide clearance was 1.5-fold reduced as compared with control values. Human immunodeficiency virus (HIV) load declined from a median baseline value of 29,000 copies/mL to a median minimum value on therapy of 500 copies/mL. CONCLUSION: Either modified-dose or full-dose CHOP chemotherapy for HIV-NHL, delivered with HAART, is effective and tolerable.

Adult↗

Soluble myelin-associated glycoprotein released from damaged white matter inhibits axonal regeneration.

The adult, mammalian CNS does not regenerate after injury largely because of a glial scar and inhibitors of regeneration in myelin. To date, two myelin inhibitors, myelin-associated glycoprotein (MAG) and Nogo, both transmembrane proteins, have been identified. No secreted inhibitors of regeneration have been described. However, a proteolytic fragment of MAG (dMAG), consisting of the entire extracellular domain, is readily released from myelin and is found in vivo. Here, we show, first, that a soluble, chimeric form of MAG (MAG-Fc), when secreted from CHO cells in a collagen gel and hence in the absence of a fixed substrate, inhibits/deflects neurite outgrowth from P6 dorsal root ganglion (DRG) neurons. This inhibition was blocked when a MAG monoclonal antibody was included in the gel and a control chimera sialoadhesin-Fc (Sn-Fc), which, like MAG, binds neurons in a sialic acid-dependent manner but does not inhibit axonal growth, had no effect. Using the same assay system we showed that factors secreted from damaged white matter inhibited/deflected neurite outgrowth. This inhibition was neutralized when a MAG monoclonal antibody was included in the gel and there was no inhibition when white matter from a MAG knockout mouse was used. Factors secreted from damaged white matter from wild-type mice had no effect on neurite outgrowth from E18 DRG neurons. These results show that factors secreted from damaged white matter inhibit axonal regeneration and that the majority of inhibitory activity can be accounted for by dMAG. Thus, released dMAG is likely to play an important role in preventing regeneration, immediately after injury before the glial scar forms.

Animals↗

A sequence change (Arg158Gln) in the leucine zipper-like motif region of the MYOC/TIGR protein.

The myocilin/trabecular meshwork-inducible glucocorticoid response (MYOC/TIGR) gene was identified as a gene that caused open angle glaucoma (OAG). Single-strand conformation polymorphism analysis and subsequent sequence analysis were performed for the MYOC/TIGR gene in 120 unrelated Japanese OAG patients with increased intraocular pressure (IOP), 116 unrelated OAG patients without increased IOP, and 106 unrelated control subjects without glaucoma. An Arg158Gln sequence change in the leucine zipper-like motif (LZM) region in the myosin-homology domain was found in 2 OAG patients with or without increased IOP, and in a 56-year-old control subject without glaucoma. This is the first report of missense sequence change in the LZM region of the MYOC/TIGR protein in subjects showing various phenotypes, including a control subject. These findings suggest that Arg158Gln in the LZM region is probably a rare nondisease-causing polymorphism, despite its important role in this region, because it was found in a control subject, although Arg158Gln was previously reported as a probable disease-causing mutation.

Adult↗

The fractal nature of Escherichia coli biological flocs.

The fractal structures of Escherichia coli biological flocs were characterised in terms of fractal dimension, which is a measurement of how the bacteria in the flocs occupy space. The dimensional analysis methods, based on power law correlations between floc perimeter, projected area and maximum length, were used to determine the one- and two-dimensional fractal dimensions (D(1) and D(2)) of E. coli flocs formed by flocculation in chitosan solution with a concentration of 10.0 mg chitosan per g dry cell weight (DCW), giving D(1)=1.07+/-0.06 and D(2)=1.70+/-0.08 (+/-S.D.). The three-dimensional fractal dimension (D(3)) of the E. coli flocs was determined by the two-slopes method, using cumulative size distributions of floc length and solid volume, to be 1.99+/-0.08 (+/-S.D.), which is close to the value of D(3)=2.14+/-0.04 (+/-S.D.) measured by the small angle light scattering method. The results demonstrate that E. coli flocs flocculated with chitosan have a fractal nature, as their fractal dimensions D(1), D(2) and D(3) differ from the values of 1, 2 and 3 expected for the spherical Euclidean object, respectively.

Journal Article↗

Involving of the cytoplasmic region of leukemia inhibitory factor receptor alpha subunit, IL-6 related signal transducer-gp130 or fas death domain for MAPK p42/44 activation in HL-60 cell with LIF or anti-Fas IgG.

The chimeric receptors were prepared by exchanging the cytoplasmic region between leukemia inhibitory factor (LIF) receptor alpha subunit (gp190) and the other subunit-gp130 (190/130,130/190) and separately transduced into leukemia line HL-60 (to have the wild type subunit). The purpose is to investigate which subunit for activating MAPK p42/44 in leukemia cell while the cytoplasmic region homodimerization (190cyt-190cyt, 130cyt-130cyt) was induced by LIF. The results showed that MAPK p42/44 expression level after LIF stimulation 5 h was lower in the transformants with pED 130/190 (190cyt- 190cyt) (p < 0.01) and higher in the transformants with pED 190/130 (130cyt- 130cyt) (p < 0.05) than those in the parent cells. Meanwhile, MAPK p42/44 phosphorylation (Thr202/Tyr204) was ascended and the highest at 10 min in the 190/130 and descended in the 130/190. It suggests that gp130 activate MAPK p42/44 and gp190 indirectly regulate its expression and function. In order to analyses the relation of the subunit oligomerization and MAPK p42/44 we also prepared the recombination of the extracellular and transmembrane region of Fas and the cytoplasmic region of each LIFR subunit (Fas/190, Fas/130). After transduction into HL-60 with lipofection and induction by anti-Fas IgG, we found that MAPK p42/44 expression levels were lower in the Fas/190 than in the Fas/130 and parent cells (p < 0.01) and no difference between the Fas/130 and the wild type receptor. However, phospho-MAPK p42/44 were increased in the Fas/130 than the parent cells. It suggests that the oligomerization of the cytoplasmic regions of gp130 be potential to normally initiate MAPK p42/44 for the signal of HL-60 proliferation. We also determine that the separated oligomerization FasDD (no dimerization) can initiate the corresponding signal molecules, then regulate MAPK p42/44 expression and phosphorylation in leukemia cells.

Antigens, CD↗

Eukaryotic elongation factor 2 can bind to the synthetic oligoribonucleotide that mimics sarcin/ricin domain of rat 28S ribosomal RNA.

Eukaryotic elongation factor 2 (eEF2) catalyzes the translocation of peptidyl-tRNA from the A site to P site by binding to the ribosome. In this work, the complex formation of rat liver eEF2 with a synthetic oligoribonucleotide (SRD RNA) that mimics sarcin/ricin domain of rat 28S ribosomal RNA is invested in vitro. Purified eEF2 can specifically bind SRD RNA to form a stable complex. tRNA competes with SRD RNA in binding to eEF2 in a less extent. Pretreatment of eEF2 with GDP or ADP-ribosylation of eEF2 by diphtheria toxin can obviously reduce the ability of eEF2 to form the complex with the synthetic oligoribonucleotide. These results indicate that eEF2 is likely to bind directly to the sarcin/ricin domain of 28S ribosomal RNA in the process of protein synthesis.

Adenosine Diphosphate Ribose↗

Analysis of myocilin gene mutations in Japanese patients with normal tension glaucoma and primary open-angle glaucoma.

The myocilin gene was identified as a gene (MYOC) that caused primary open-angle glaucoma (POAG). Although a normal tension glaucoma (NTG) patient with the myocilin gene mutation was previously reported, no study using large numbers of patients with NTG has been reported. Single-strand conformation polymorphism analysis and subsequent sequence analysis were performed for genotyping the myocilin gene in 114 unrelated Japanese patients with NTG. One hundred and nineteen patients with POAG and 100 control subjects without glaucoma were studied as reference subjects. Five amino acid sequence changes of the myocilin were identified: Arg46Stop (one NTG), Arg76Lys (four NTG, 10 POAG, seven control), Arg158Gln (one NTG, one POAG, one control) found in only Japanese, Asp208Glu (four NTG, three POAG, one control), Pro481Ser (one control). Pro481Ser was novel. Arg76Lys always occurred with 1-83 from G to A in the promoter as it was reported in Chinese. Although some Japanese patients with NTG had sequence changes of the myocilin gene, there were no apparent specific mutations in patients with NTG.

Adolescent↗

Differential judgement of static facial expressions of emotions in three cultures.

Judging facial expressions of emotions has important clinical value in the assessment of psychiatric patients. Judging facial emotional expressions in foreign patients however, is not always easy. Controversy has existed in previous reports on cultural differences in identifying static facial expressions of emotions. While it has been argued that emotional expressions on the face are universally recognized, experimental data obtained were not necessarily totally supportive. Using the data reported in the literature, our previous pilot study showed that the Japanese interpreted many emotional expressions differently from USA viewers of the same emotions. In order to explore such discrepancies further, we conducted the same experiments on Chinese subjects residing in Beijing. The data showed that, similar to the Japanese viewers, Chinese viewers also judged many static facial emotional expressions differently from USA viewers. The combined results of the Chinese and the Japanese experiments suggest a major cross-cultural difference between American and Asian viewers in identifying some static facial emotional expressions, particularly when the posed emotion has negative connotations. The results have important implications for cross-cultural communications when facial emotional expressions are presented as static images.

Adult↗

Transferrin but not albumin mediates stimulation of complement C3 biosynthesis in human proximal tubular epithelial cells.

Complement is increasingly implicated in the pathogenesis of progressive renal disease resulting from persistent proteinuria. We have previously shown that apical serum proteins stimulate C3 in cultured human proximal tubular epithelial cells (PTECs), and that the stimulant is a nonalbumin compound of 30 to 100 kd. We postulated in this study that transferrin and apotransferrin, also important components of proteinuric urine in this molecular-weight range, might be the culprit. Human PTECs were obtained by differential sieving of renal cortical tissue from the normal pole of tumor nephrectomy specimens and characterized to be predominantly of proximal tubular origin. Complement C3 messenger RNA (mRNA) expression was analyzed in confluent growth-arrested PTEC monolayers in media containing different concentrations (2.5 to 20 mg/mL) of transferrin by reverse transcription and polymerase chain reaction. Pure human albumin was used as a control protein. C3 protein secretion was detected and quantified by a sandwich enzyme-linked immunosorbent assay on cell culture supernatants after distinct time points. Transferrin enhanced the rate of C3 secretion in a dose-dependent manner, reaching maximal stimulation at doses of 10 mg/mL. Selected experiments using the Transwell technique showed that C3 release was predominantly apical in the resting state. The addition of 10 mg/mL of transferrin apically but not basolaterally stimulated both apical and basolateral C3 secretion and increased the basolateral-apical ratio of C3 secretion from 0.45 +/- 0.16 to 0.93 +/- 0.24 (P: < 0.02). Constitutive C3 mRNA expression was upregulated by transferrin in a time- and dose-dependent fashion, reaching a peak after 24 hours. A similar degree of C3 upregulation was reproduced when iron-poor transferrin, apotransferrin, was used instead. These results indicate that C3 synthesis in PTECs is upregulated by transferrin, for which protein rather than iron moiety may account for the observed effects. These findings provide evidence linking proteinuria with overexpression of tubular complement.

Apoproteins↗

In vitro studies of aquaporins 1 and 3 expression in cultured human proximal tubular cells: upregulation by transferrin but not albumin.

Dysregulated renal water handling is a cardinal feature of nephrotic syndrome that has been shown in animal models of experimental nephrosis to mediate renal aquaporin (AQP) expression. However, data on the effect of proteinuria on the proximal tubule, which is heavily vested with AQP1 and therefore may participate in water homeostasis, are limited. To investigate this, we exposed primary human proximal tubular epithelial cells (PTECs) to two key proteinuric components shown to perturb tubule function: human serum albumin and transferrin. Using reverse-transcriptase polymerase chain reaction and immunocytochemical techniques, PTECs in the quiescent state were found to express AQP3 in addition to AQP1 gene and protein, which was also validated in a human proximal tubule cell line, HK-2. Immunohistochemical staining localized AQP1 synthesis to the apical and basolateral membranes and AQP3 synthesis to the basolateral membrane of proximal tubule epithelium. Transferrin in doses reaching nephrotic range upregulated PTEC transcription and translation of both AQP1 and AQP3 in a time- and dose-dependent manner. After 24 hours of stimulation, transferrin led to a 2.4- and 2.2-fold increase in AQP1 and APQ3 messenger RNA expression, whereas protein synthesis surged by 40.7% +/- 2.48% and 24.2% +/- 0.9% compared with control, respectively. These effects were not observed with albumin challenge and were not caused by osmolality fluctuation with transferrin treatment. In summary, our novel finding of AQP3 in PTECs indicates a role for AQP3 in proximal tubule water reabsorption. The pathophysiological significance of heightened AQP1 and AQP3 expression in PTECs on protein challenge as occurs in the nephrotic state requires further investigation.

Albumins↗

Tuberculosis infection in Chinese patients undergoing continuous ambulatory peritoneal dialysis.

A retrospective study of the prevalence and pattern of tuberculosis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) was performed. Thirty-eight cases of tuberculosis were diagnosed among 790 patients (18 men, 20 women; mean age, 58 +/- 12.6 years) between July 1994 and June 2000. The interval between the initiation of CAPD and onset of tuberculosis ranged from 1 to 168 months (median, 22 months). There were 18 cases of pulmonary tuberculosis, 14 cases of tuberculous peritonitis, 5 cases of tuberculous lymphadenitis, and 1 case of tuberculous synovitis. Patients with pulmonary tuberculosis usually presented with fever, constitutional symptoms, and pleural effusion or pulmonary infiltrates on chest radiograph. Abdominal pain and turbid dialysate were the main presenting symptoms in patients with tuberculous peritonitis. Diagnosis was established by positive culture in 20 patients, typical histological characteristics on a tissue biopsy specimen in 10 patients, and response to empirical antituberculous treatment in 8 patients. The duration of symptoms before the diagnosis of tuberculosis and initiation of antituberculous treatment ranged from 7 to 57 days (median, 30 days). Antituberculous treatment consisted of isoniazid, rifampicin, pyrazinamide, and ofloxacin for 9 to 15 months. Antituberculous treatment generally was well tolerated. Twenty-seven patients (71%) completed antituberculous treatment. No recurrence of tuberculosis was observed after a mean follow-up of 19.8 months. Eleven patients (29%) died while on antituberculous treatment; none of the deaths appeared to be directly caused by tuberculosis. We conclude that: (1) tuberculosis is prevalent among CAPD patients in our locality; (2) extrapulmonary tuberculosis, particularly tuberculous peritonitis, is common; and (3) a high index of suspicion for tuberculosis among CAPD patients is warranted to ensure early diagnosis and prompt initiation of treatment.

Aged↗

Majocchi's granuloma and posttransplant lymphoproliferative disease in a renal transplant recipient.

Renal transplant recipients are predisposed to infection and malignancy because of underlying long-term immunosuppressive therapy. In this case report, a renal transplant patient with coexisting Trichophyton rubrum granuloma (Majocchi's granuloma) and posttransplant lymphoproliferative disease (PTLD) is presented, showing the undesirable effects of heavy immunosuppression. Majocchi's granuloma was probably associated with PTLD as a reflection of overimmunosuppression.

Adult↗

Development and applications of a complete set of rice telotrisomics.

We previously isolated a complete set of primary trisomics along with many other aneuploids from triploid plants derived from an indica rice variety "Zhongxian 3037." About 30,000 progeny from these trisomic and aneuploid plants were grown each year from 1994 to 1999. The variants that differed morphologically from both the diploids and the original primary trisomics were collected for cytological identification. From these variants, a complete set of telotrisomics covering all 24 rice chromosome arms was obtained. The identities of the extra chromosomes were further confirmed by dosage analysis of the RFLP markers on extra chromosome arms. The telocentric nature of the extra chromosomes in these stocks was verified by fluorescence in situ hybridization (FISH) using a rice centromeric BAC clone as a marker probe. In general, the shorter the extra chromosome arm of a telotrisomic, the stronger the resemblance it bears to the diploid; the longer the extra chromosome arm, the stronger the resemblance to the corresponding primary trisomic. We demonstrated that DNA clones can be rapidly assigned to specific chromosome arms by dosage analysis with the telotrisomics. We also showed that telotrisomics are valuable tools for chromosome microdissection and for developing chromosome-specific DNA markers.

Chromosomes↗

Changing access to health services in urban China: implications for equity.

The ongoing reform of public institutions and state-owned enterprises in urban China has had a profound impact on the financing, organization and provision of health services. Access to health care by the urban population has become more inequitable. One of the most pressing concerns is that those who have lost jobs have increasing difficulties accessing health care. Using the data from the national household health surveys conducted in 1993 and 1998, this paper presents empirical results of changing utilization of health care among different income groups. Over 16 000 households and 54 000 individuals in the urban areas were randomly selected to collect information on perceived need of and demand for health care and expenditures on the services. The findings show that the income gap between the highest and lowest income groups increased in real terms from 1993 to 1998. There was a significant decline in the population covered by the government insurance scheme (GIS) and the labour insurance scheme (LIS), while the proportion of the population who had to pay for services out-of-pocket increased from 28% in 1993 to 44% in 1998. There was no statistically significant change in self-reported illness in the 2 weeks prior to survey among the study population over the period. While it was found that more people who reported illness from each income group received medical treatment of some kind, there was a decline in seeking care from a health provider. Among those in the lowest income group who reported illness but did not obtain treatment of any kind, nearly 70% (as compared with 38% in 1993) claimed financial difficulty as the major reason in 1998. The use of in-patient services dropped significantly from 4.5% in 1993 to 3.0% in 1998. The decreased use of in-patient services was more serious in the lowest and lower income groups than in higher and highest income groups. The percentage of patients referred for hospital admission but not being hospitalized had a negative relationship with income level. We can conclude from the data analysis that access of the urban population, particularly the poor, to formal health services has worsened and become more inequitable since the early 1990s. Among possible reasons for this trend are the rapid rise of per capita expenditure on health services and the decline in insurance coverage.

China↗

A streamlined process to phenotypically profile heterologous cDNAs in parallel using yeast cell-based assays.

To meet the demands of developing lead drugs for the profusion of human genes being sequenced as part of the human genome project, we developed a high-throughput assay construction method in yeast. A set of optimized techniques allows us to rapidly transfer large numbers of heterologous cDNAs from nonyeast plasmids into yeast expression vectors. These high- or low-copy yeast expression plasmids are then converted quickly into integration-competent vectors for phenotypic profiling of the heterologous gene products. The process was validated first by testing proteins of diverse function, such as p38, poly(ADP-ribose) polymerase-1, and PI 3-kinase, by making active-site mutations and using existing small molecule inhibitors of these proteins. For less well-characterized genes, a novel random mutagenesis scheme was developed that allows a combination selection/screen for mutations that retain full-length expression and yet reverse a growth phenotype in yeast. A broad range of proteins in different functional classes has been profiled, with an average yield for growth interference phenotypes of approximately 30%. The ease of manipulation of the yeast genome affords us the opportunity to approach drug discovery and exploratory biology on a genomic scale and shortens assay development time significantly.

Amino Acid Sequence↗