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Biomedical subjects

J Tian

Publications and source records attributed to J Tian.

At least 73 records · Page 4Linked to original sources

Testing quasi-visual neurons in the monkey's frontal eye field with the triple-step paradigm.

To look successively at sites where several spots of light have appeared in the dark, we cannot simply rely on the image left by these targets on our retina. Our brain has to update target coordinates by taking into account each gaze movement that has taken place. A particular type of brain cell--the quasi-visual (QV) neuron--is assumed to play an important role in this updating by combining target coordinates and eye displacement signals. However, what is exactly this role? Is a QV neuron an element of a working memory that encodes the location of a potential target, or is it pointing to the location of the single goal selected for the next saccade? The two roles theoretically correspond to successive stages of processing: the locations of the optional targets would be stored at one stage, whereas the location of the next selected target would be stored at the subsequent stage. With a task that imposes a choice of goals--the triple-step paradigm--we found evidence that several groups of QV neurons can become simultaneously activated in the monkey's frontal eye field (FEF), suggesting that each group represents a different target location. This supports the hypothesis that the FEF itself contains the spatial information about not yet selected targets.

Animals↗

Vestibular catch-up saccades in labyrinthine deficiency.

During rapid head rotations, saccades ipsiversive with compensatory vestibulo-ocular reflex (VOR) slow phases may augment the deficient VOR and assist gaze stabilization in space. The present experiments compared these vestibular catch-up saccades (VCUSs) with visually and memory-guided saccades. To characterize VCUSs and their relationship to deficiency of the initial VOR, we delivered random, whole-body transients of 1000 and 2800 degrees/s2 peak yaw acceleration around four different eccentric vertical axes in eight unilaterally and one bilaterally vestibulopathic subjects, as well as nine age-matched normal subjects. Eye and head movements were sampled at 1200 Hz using magnetic search coils. Subjects fixed targets at either 500 or 15 cm distance immediately before unpredictable onset of rotation in darkness. Under all testing conditions, normal subjects exhibited only compensatory vestibular slow phases and occasional anticompensatory quick phases. This behavior was also typical of unilaterally vestibulopathic subjects rotated contralesionally. When rotated ipsilesionally, however, vestibulopathic subjects had deficient slow-phase VOR gain with prolonged latency, and six of the nine exhibited saccadic movements in the compensatory direction (VCUSs). Higher head accelerations preferentially evoked VCUSs, but there were no preferred combinations of target distances and eccentric rotation axes. Peak velocities and durations of VCUSs increased with saccade amplitude. The latency distribution for VCUSs peaked around 70 ms, substantially shorter than reported for either visually guided express saccades or vestibular memory contingent saccades. The latency of each VCUS was highly correlated with the gaze error prior to that VCUS. The amplitude of VCUSs was calibrated to gaze position error, such that VCUSs reduced gaze error by an average of 37%. Thus when VOR slow-phase responses cannot compensate fully for head rotation, vestibular gaze position error can nevertheless calibrate the programming of VCUSs to augment the deficient VOR, much like catch-up saccades substitute for deficient visual pursuit.

Acceleration↗

The excretion of biotrace elements using the multitracer technique in tumour-bearing mice.

A radioactive multitracer solution obtained from the nuclear reaction of selenium with 25 MeV/nucleon 40Ar ions was used for investigation of trace element excretion into the faeces and urine of cancerous mice. The excretion rates of 22 elements (Na, K, Rb, Mg, Ca, Sr, Ga, As, Sc, V, Cr, Mn, Co, Fe, Y, Zr, Mo, Nb, Tc, Ru, Ag and In) were simultaneously measured under strictly identical experimental conditions, in order to clarify the excretion behavior of these elements in cancerous mice. The faecal and urinary excretion rates of Mg, Sr, Ga, As, Sc, V, Cr, Mn, Co, Fe, Y, Zr, Nb, Ru and Mo in cancerous mice, showed the in highest value at 0-8 hours. The accumulative excretion of Ca, Mo, Y and Zr was decreased and Na, Fe, Mn and Co increased in tumour-bearing mice, when compared to normal mice.

Animals↗

The CD28-related molecule ICOS is required for effective T cell-dependent immune responses.

While CD28 is critical for expansion of naive T cells, recent evidence suggests that the activation of effector T cells is largely independent of CD28/B7. We suggest that ICOS, the third member of the CD28/CTLA-4 family, plays an important role in production of IL-2, IL-4, IL-5, and IFNgamma from recently activated T cells and contributes to T cell-dependent B help in vivo. Inhibition of ICOS attenuates lung mucosal inflammation induced by Th2 but not Th1 effector populations. Our data indicate a critical function for the third member of the CD28 family in T cell-dependent immune responses.

Abatacept↗

Regulation of Na/K-ATPase beta1-subunit gene expression by ouabain and other hypertrophic stimuli in neonatal rat cardiac myocytes.

Partial inhibition of Na/K-ATPase by ouabain causes hypertrophic growth and regulates several early and late response genes, including that of Na/K-ATPase alpha3 subunit, in cultured neonatal rat cardiac myocytes. The aim of this work was to determine whether ouabain and other hypertrophic stimuli affect Na/K-ATPase beta1 subunit gene expression. When myocytes were exposed to non-toxic concentrations of ouabain, ouabain increased beta1 subunit mRNA in a dose- and time-dependent manner. Like the alpha3 gene, beta1 mRNA was also regulated by several other well-known hypertrophic stimuli including phenylephrine, a phorbol ester, endothelin-1, and insulin-like growth factor, suggesting involvement of growth signals in regulation of beta1 expression. Ouabain failed to increase beta1 subunit mRNA in the presence of actinomycin D. Using a luciferase reporter gene that is directed by the 5'-flanking region of the beta1 subunit gene, transient transfection assay showed that ouabain augmented the expression of luciferase. These data support the proposition that ouabain regulates the beta1 subunit through a transcriptional mechanism. The effect of ouabain on beta1 subunit induction, like that on alpha3 repression, was dependent on extracellular Ca2+ and on calmodulin. Inhibitions of PKC, Ras, and MEK, however, had different quantitive effects on ouabain-induced regulations of beta1 and alpha3 subunits. The findings show that partial inhibition of Na/K-ATPase activates multiple signaling pathways that regulate growth-related genes, including those of two subunit isoforms of Na/K-ATPase, in a gene-specific manner.

Adenoviridae↗

A prospective study of Tc-99m MIBI in the differential diagnosis of pelvic masses in female patients.

PURPOSE: This study evaluated the feasibility of Tc-99m MIBI scintigraphy in the differential diagnosis of pelvic masses in female patients before operation. METHODS: Seventy-one patients with pelvic masses were studied with planar imaging over the abdomen and pelvis 5, 15, 30, and 60 minutes after injection of 740 MBq (20 mCi) Tc-99m MIBI. The uptake of the masses was graded, and other abnormal signs, such as intestinal involvement, lymph node involvement, or peritoneal fluid collection, were also considered in image interpretation. An exploratory laparotomy was performed 3 days to 2 weeks after imaging. The scintigraphic diagnosis was compared with that of computed tomography (CT), CA-125 measurement, and pathologic analysis. RESULTS: Forty-one of 46 pelvic masses with no activity were proved benign. Eighteen of 25 with a fixed, focal uptake were malignant. In 19 of 23 masses, intestinal activity noted within 30 minutes was caused by metastases. All three cases with lymph node involvement and six cases with ascites were confirmed malignant. Combining focal uptake with intestinal involvement correctly indicated 22 of 23 malignant conditions before operation, whereas negative scans identified 41 of 48 benign lesions. Four of seven false-positive lesions had a higher cellular component. The diagnostic performance of Tc-99m MIBI is better than that of CT and CA-125 tests, because CT had eight false-positive and three false-negative results, whereas CA-125 had 12 false-positive and 3 false-negative results, respectively. CONCLUSIONS: Tc-99m MIBI is useful for differentiating benign and malignant pelvic masses in female patients. A fixed focal uptake or intestinal uptake of the radiotracer suggests malignancy, with diagnostic sensitivity, specificity, accuracy, and positive and negative predictive values of 95.6%, 85.4%, 88.7%, 75.9%, and 97.6%, respectively, in the current prospective study.

Adolescent↗

Interleukin-12 induces gene expression in interleukin-2 stimulated human T lymphocytes.

IL-12 is a critical immunoregulatory cytokine that promotes cell-mediated immune responses by inducing the differentiation of Th1 cells. To better clarify the molecular basis of IL-12 action, we compared the gene expression in human T lymphocytes activated by IL-2 and IL-12. mRNAs from T lymphocytes activated by either IL-2 alone or IL-2 plus IL-12 were transcribed into cDNAs. A differential mRNA display was conducted. As a result, differential display of five cDNA fragments was obtained. Sequence analysis suggests that they had high homology with recorded genes as found by a computer search against GenBank. Two full genes of the five fragments were cloned, which activation-induced C-type lectin and glucose transporter-like protein. Interestingly, these proteins were expressed in the T cells stimulated by IL-2 and IL-12, but not in the T cells stimulated by IL-2 alone. These results suggest that C-type lectin and glucose transporter-like protein may play an important role in the T lymphocyte activation induced by IL-12.

Base Sequence↗

Asymmetry of ocular motor and perceptual vestibular processing in humans with unilateral vestibular deafferentation.

To investigate the effect of asymmetrical vestibular input on the perceived straight-ahead direction, we compared 7 subjects (age 59 +/- 8 yrs, mean +/- SD) who had chronic (>10 mos) unilateral vestibular deafferentation with 10 age matched controls (age 61+/-6 younger controls (age 28 +/- 7 yrs). Despite the age difference, the two control groups performed similarly and were therefore pooled. Eye and head movements were recorded using search coils as subjects underwent 30 s trials of sinusoidal, whole body oscillation (0.4-2 Hz, peak velocities 0-120 degrees /s) in darkness while attempting to maintain gaze on a remembered target 5 m distant. As a control, most stimulus oscillations were randomly superimposed on an imperceptible, constant velocity of +/-0.5 degrees /s that produced a whole-body offset of 15 degrees by the end of the trial. Following oscillation, subjects remained motionless in darkness and were asked to orient both gaze and a manipulandum to the remembered target location. In control subjects, mean final gaze and manipulandum positions were within 15 degrees of the target for all testing conditions. There was no dependence of final gaze and manipulandum positions on the frequency or velocity of the preceding whole-body oscillations (p > 0.05). In four of seven unilaterally deafferented subjects there was an ipsilesional bias of final eye position of > or =10 degrees. These subjects moved both eye and manipulandum to the ipsilesional side, with the error increasing at higher stimulus velocities. For the 120 degrees /s peak head velocity, mean ipsilesional gaze bias ranged from 10-37 degrees and mean manipulandum bias ranged from 26-108 degrees. Although the errors depended on velocity p < 0.01), errors were independent of frequency (p > 0.1). In the remaining three subjects with vestibular deafferentation, final gaze and manipulandum positions [were not statistically different from controls.] Early gain (eye velocity / head velocity) of the VOR averaged 0.82 +/- 0.01 for the first 10 s of all trials and was similar in all groups (p > 0.1). Gain during the final 10 s gain averaged 0.78 +/- 0.01 for control subjects, but was significantly lower at 0.70 +/- 0.01 for unilaterally deafferented subjects, whose eye positions reached the limit of the ocular motor range. We conclude that many humans with chronic unilateral vestibular deafferentation have a large ipsilesional dynamic bias of eye position and the perceived straight ahead direction reflecting persistent asymmetry of vestibular processing.

Adult↗

Fractionated radioimmunotherapy using low doses of iodine-131 labeled anti-CEA monoclonal antibody after tumor volume reduction.

OBJECTIVE: To assess the efficacy of fractionated administration of radiolabeled monoclonal antibody in the treatment of metastases after tumor volume reduction surgery, various experimental therapies were studied comparatively. METHODS: A total of 200 inbred mice received tumor implantation from a murine adenocarcinoma cell line. The mice were randomly grouped to give saline, Arc-a, 131I-C50 in single or fractionated doses, cold C50, or non-specific 131I-IgG with or without surgical removal of the implanted tumor xenograft. RESULTS: In comparison to controls, animals receiving Arc-a and radioactive agents had longer survival, smaller tumor, better clinical condition, and less metastases foci. The best therapeutic response was noted after fractionated doses of 131I-C50, which showed better results in every aspect than those treated with other modalities. The favorable outcome was even more pronounced after tumor volume reduction. CONCLUSIONS: Fractionated dosing may improve the deposition of radiolabeled monoclonal antibody (McAb) and provide the best therapeutic effect on implanted tumor and metastases. Thus fractionated radioimmunotherapy (RIT) after tumor volume reduction might be a practical method with promising therapeutic results.

Animals↗

[The construction of a recombined E. coli strain with stable and high production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate)].

Plasmid pJMC2 was constructed by cloning the parDE fragment of RK2 into pTZ18U-PHB which harbored phaCAB from Alcaligenes eutrophus and was transferred into E. coli HMS174 and E. coli JM107 separately. It is very stable in its hosts cultured in medium without ampicillin. E. coli HMS 174(pTZ18U-PHB) and E. coli JM107(pTZ18U-PHB) produced P(3HB-co-3HB) in a low phosphate concentration medium(18 mmol/L). The proportion of 3-hydroxyvalerate(3HV) in the polymer was 5%-8%. A fed-batch culture of E. coli HMS174(pJMC2) was conduct in a 5 L automatically controlled fermentor, the final dry cell weight, P(3HB-co-3HV) content, and th 3HV proportion were 42.5 g/L, 70% and 4.9% respectively.

Culture Media↗

[Positron emission tomography of tinnitus-related brain areas].

OBJECTIVE: To map the tinnitus specific central activity and foci site in brain and to investigate the effects of hearing loss, tinnitus side, right or left handed on foci site. METHODS: Glucose metabolic activity of brain was studied with positron emission tomography (PET) using 18F-FDG as radiotracer. Seventeen patients with severe tinnitus and fifteen control subjects participated in this study. All subjects were fell into four groups according to their hearing levels. There were 13 tinnitus patients with hearing loss in Group one, 4 tinnitus patients without hearing loss in Group two, 2 control subjects with hearing loss in Group three and 13 control subjects without hearing loss in Group four. Statistical parameters mapping (SPM) was used to analyze the PET data and to determine the Brodmann area (BA) according to Talairach coordinate system. RESULTS: Increase of neuronal activity caused by tinnitus occurred predominately in the left hemisphere with significant foci in the transverse temporal gyrus (BA41), superior temporal gyrus (BA42, 22), anterior middle temporal gyrus (BA38) and hippocampus. Bilateral hemispheres were concerned with the neuronal activity caused by hearing loss while foci site were located at the posterior superior temporal gyrus(BA42,22), medial portion of middle temporal gyrus(BA21), combined auditory area(BA39). Left middle frontal gyrus (BA8, 9) as well as left inferior frontal gyrus(BA45) were also link up with hearing loss. CONCLUSION: As a new path in research, PET has provided an objective evidence for tinnitus and may be used as a potential tool in objectively measuring tinnitus. Tinnitus-related brain areas and their influence factors were discussed.

Adolescent↗

[Bone mineral density and exercises: a cross-sectional study on Chinese athletes].

OBJECTIVES: To evaluate the effect of exercise to osteoporosis by bone mineral density (BMD) measurement of athelets comparing normal individuals in general population. METHODS: BMD of radium, lumber spine, and femoral neck were measured by single photon absorptiometry (SPA), quantitative CT (QCT), and dual X-ray absorptiometry (DXA) respectively in athletes (n = 162, male 79, female 83) and age matched non-athletes normal population (n = 204, male 91, female 113) in Beijing. RESULTS: BMD of all sites in all age groups of both male and female athletes are significantly higher comparing with that in non-athletic population. This predominance in athletes is even more distinctive in peak bone mass. Peak bone mass of male athletes is significantly higher than that of female athletes. Bone loss with age is less apparent in athletes than in control. However, there is an accelerated decline of BMD in lumber spine and femoral neck in 30-39 year age group in both male and female athletes, which may be due to the wanting of physical exercise. CONCLUSIONS: Long term regular proper exercise started in adolescence may play a very important role in the prevention of osteoporosis by improving peak bone mass and decreasing bone loss.

Absorptiometry, Photon↗

Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses.

T1/ST2 is an orphan receptor of unknown function that is expressed on the surface of murine T helper cell type 2 (Th2), but not Th1 effector cells. In vitro blockade of T1/ST2 signaling with an immunoglobulin (Ig) fusion protein suppresses both differentiation to and activation of Th2, but not Th1 effector populations. In a nascent Th2-dominated response, anti-T1/ST2 monoclonal antibody (mAb) inhibited eosinophil infiltration, interleukin 5 secretion, and IgE production. To determine if these effects were mediated by a direct effect on Th2 cells, we next used a murine adoptive transfer model of Th1- and Th2-mediated lung mucosal immune responses. Administration of either T1/ST2 mAb or T1/ST2-Ig abrogated Th2 cytokine production in vivo and the induction of an eosinophilic inflammatory response, but failed to modify Th1-mediated inflammation. Taken together, our data demonstrate an important role of T1/ST2 in Th2-mediated inflammatory responses and suggest that T1/ST2 may prove to be a novel target for the selective suppression of Th2 immune responses.

Allergens↗

Stimulation of Elk1 transcriptional activity by mitogen-activated protein kinases is negatively regulated by protein phosphatase 2B (calcineurin).

Cellular calcium (Ca2+) and the Ca2+-binding protein calmodulin (CaM) regulate the activities of Ca2+/CaM-dependent protein kinases and protein phosphatase 2B (calcineurin). Functional interactions between CaM kinases and mitogen-activated protein (MAP) kinases were described. In this report, we describe cross-talk between calcineurin and mitogen-activated protein kinase signaling. Calcineurin was found to specifically down-regulate the transcriptional activity of transcription factor Elk1, following stimulation of this activity by the ERK, Jun N-terminal kinase, or p38 MAP kinase pathways. Expression of constitutively activated calcineurin or activation of endogenous calcineurin by Ca2+ ionophore decreased the phosphorylation of Elk1 at sites that positively regulate its transcriptional activity. Calcineurin specifically dephosphorylates Elk1 at phosphoserine 383, a site whose phosphorylation by MAP kinases makes a critical contribution to the enhanced transcriptional activity of Elk1. The cross-talk between calcineurin and MAP kinases is of physiological significance as low doses of Ca2+ ionophore which by themselves are insufficient for c-fos induction can actually inhibit induction of c-fos expression by activators of MAP kinases. Thus through the effect of calcineurin on Elk1 phosphorylation, Ca2+ can have a negative effect on expression of Elk1 target genes. This mechanism explains why different levels of intracellular Ca2+ can result in very different effects on gene expression.

Acetyltransferases↗

GABA(A) receptors mediate inhibition of T cell responses.

We describe the presence of functional GABA(A) receptors on T cells. GABA inhibited anti-CD3 and antigen-specific T cell proliferation in vitro in a dose-dependent manner that was 1) mimicked by the GABA(A) receptor agonist muscimol (but not the GABA(B) receptor agonist baclofen), 2) blocked by GABA(A) receptor antagonists and a GABA(A) receptor Cl- channel blocker (picrotoxin) and 3) enhanced by pentobarbital. These data suggest that GABA(A) receptors mediate this immune inhibition and that these receptors can be modulated in a similar fashion to their neuronal counterparts. Finally, GABA inhibited DTH responses in vivo. Thus, pharmacological modulation of GABA(A) receptors may provide new approaches to modulate T cell responses in inflammation and autoimmune disease.

Amidines↗

Control of cell cycle progression by c-Jun is p53 dependent.

The c-jun proto-oncogene encodes a component of the mitogen-inducible immediate-early transcription factor AP-1 and has been implicated as a positive regulator of cell proliferation and G1-to-S-phase progression. Here we report that fibroblasts derived from c-jun-/- mouse fetuses exhibit a severe proliferation defect and undergo a prolonged crisis before spontaneous immortalization. The cyclin D1- and cyclin E-dependent kinases (CDKs) and transcription factor E2F are poorly activated, resulting in inefficient G1-to-S-phase progression. Furthermore, the absence of c-Jun results in elevated expression of the tumor suppressor gene p53 and its target gene, the CDK inhibitor p21, whereas overexpression of c-Jun represses p53 and p21 expression and accelerates cell proliferation. Surprisingly, protein stabilization, the common mechanism of p53 regulation, is not involved in up-regulation of p53 in c-jun-/- fibroblasts. Rather, c-Jun regulates transcription of p53 negatively by direct binding to a variant AP-1 site in the p53 promoter. Importantly, deletion of p53 abrogates all defects of cells lacking c-Jun in cell cycle progression, proliferation, immortalization, and activation of G1 CDKs and E2F. These results demonstrate that an essential, rate-limiting function of c-Jun in fibroblast proliferation is negative regulation of p53 expression, and establish a mechanistic link between c-Jun-dependent mitogenic signaling and cell-cycle regulation.

3T3 Cells↗

Xenopus laevis sperm receptor gp69/64 glycoprotein is a homolog of the mammalian sperm receptor ZP2.

Little is known about sperm-binding proteins in the egg envelope of nonmammalian vertebrate species. We report here the molecular cloning and characterization of a recently identified sperm receptor (gp69/64) in the Xenopus laevis egg vitelline envelope. Our data indicate that the gp69 and gp64 glycoproteins are two glycoforms of the receptor and have the same number of N-linked oligosaccharide chains but differ in the extent of O-glycosylation. The amino acid sequence of the receptor is closely related to that of the mouse zona pellucida protein ZP2. Most of the sequence conservation, including a ZP domain, a potential furin cleavage site, and a putative transmembrane domain are located in the C-terminal half of the receptor. Proteolytic cleavage of the gp69/64 protein by a cortical granule protease during fertilization removes 27 amino acid residues from the N terminus of gp69/64 and results in loss of sperm binding to the activated eggs. Similarly, we find that treatment of eggs with type I collagenase removes 31 residues from the N terminus of gp69/64 and has the same effect on sperm binding. The isolated and purified N terminus-truncated receptor protein is inactive as an inhibitor of sperm-egg binding. Earlier studies on the effect of Pronase digestion on receptor activity suggest that this N-terminal peptide may contain an O-linked glycan that is involved in the binding process. Based on these results and the findings on the primary structure of the receptor, a pathway for the maturation and secretion of gp69/64, as well as its inactivation following fertilization, is proposed.

Amino Acid Sequence↗