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Biomedical subjects

J Cui

Publications and source records attributed to J Cui.

At least 145 records · Page 8Linked to original sources

Sympathetic nerve response to muscle during anteroposterior acceleration in humans.

This study aimed to elucidate the effects of linear acceleration on muscle sympathetic nerve activity (MSNA) in humans. Eight healthy young male volunteers were seated in a linear accelerator (sled) during the recording of their electrocardiogram, blood pressure with the Finapres, thoracic impedance and respiration curve. MSNA was recorded from the tibial nerve by microneurography. At a fixed distance of sled movements in an anteroposterior direction, eight modes of stimulation with peak accelerations at 0.05, 0.10, 0.15, and 0.20 G (gravity) in sinusoidal or step mode were applied to each subject. Each movement was repeated for 5 cycles. Both the total activity and the burst rate of MSNA decreased during acceleration, and the level of the decrease was proportional to the level of the acceleration, whereas the average heart rate, thoracic impedance and mean arterial pressure did not change significantly. These results suggests that moderate linear acceleration may suppress MSNA in humans.

Acceleration↗

[Time resolved photoluminescence of PPV derivatives/C60 combination system].

We report the integrated and picosecond time-resolved photoluminescence (TRPL) measurement from two kinds of combination films: Poly(2-methoxy-5-(4-butenyloxy)phenylene vinylene) (MB-PPV)/C60 and Poly (2-methoxy-5-(4'-bromo-butoxy) phenylene vinylene) (MBB-PPV)/C60. Comparing with the pure MBB-PPV film, PL weakening and quenching of MBB-PPV were observed in the multilayer and mixed MBB-PPV/C60 films respectively. From TRPL spectra, the change of PL decay lifetime could be clearly seen, those could be attributed to the excitation transfer (ET) process between the excited MBB-PPV molecule and C60 molecule. Further measurements indicate that there is no noticeable dependence of the ET process on the temperature in the combination films.

English Abstract↗

Requirement for Valpha14 NKT cells in IL-12-mediated rejection of tumors.

A lymphocyte subpopulation, the Valpha14 natural killer T (NKT) cells, expresses both NK1.1 and a single invariant T cell receptor encoded by the Valpha14 and Jalpha281 gene segments. Mice with a deletion of the Jalpha281 gene segment were found to exclusively lack this subpopulation. The Valpha14 NKT cell-deficient mice could no longer mediate the interleukin-12 (IL-12)-induced rejection of tumors. Although the antitumor effect of IL-12 was thought to be mediated through natural killer cells and T cells, Valpha14 NKT cells were found to be an essential target of IL-12, and they mediated their cytotoxicity by an NK-like effector mechanism after activation with IL-12.

Animals↗

CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides.

Natural killer T (NKT) lymphocytes express an invariant T cell antigen receptor (TCR) encoded by the Valpha14 and Jalpha281 gene segments. A glycosylceramide-containing alpha-anomeric sugar with a longer fatty acyl chain (C26) and sphingosine base (C18) was identified as a ligand for this TCR. Glycosylceramide-mediated proliferative responses of Valpha14 NKT cells were abrogated by treatment with chloroquine-concanamycin A or by monoclonal antibodies against CD1d/Vbeta8, CD40/CD40L, or B7/CTLA-4/CD28, but not by interference with the function of a transporter-associated protein. Thus, this lymphocyte shares distinct recognition systems with either T or NK cells.

Animals↗

Inhibition of platelet deposition with local delivery of heparin using a double balloon catheter.

Heparin is an effective agent in the treatment of unstable angina and myocardial infarction. The clinical utility of heparin is limited by bleeding complications. This study was performed to determine whether static delivery of heparin could effectively inhibit further platelet deposition. Thrombogenic graft segments were incorporated into chronic arteriovenous shunts in pigs. Autologous platelets were labeled with 111Indium. Platelet deposition was quantitated with gamma camera imaging. The grafts were exposed to blood flow for 15 min in order to induce platelet deposition on the thrombogenic surface. Heparin was delivered locally either by direct exposure or with a double balloon catheter. After a 15 minute exposure period, the heparin solution was removed and subsequent platelet deposition was monitored for 90 minutes. Heparin, administered with the double balloon catheter in doses as low as 12.5 U, effectively inhibited further platelet deposition. An intravenous injection of 100 U of heparin, the highest dose use for local delivery, did not perturb bleeding time or the activated partial thromboplastin time. In conclusion, platelet deposition can be inhibited with static local delivery of heparin at doses that are not associated with systemic bleeding.

Animals↗

Response to vestibular stimulation of sympathetic outflow to muscle in humans.

The objective of the present study was to determine the effect of vestibular stimulation on the sympathetic outflow to muscle in humans. Fourteen healthy volunteers were studied while in the supine position with electrocardiography, blood pressure monitoring and electro-oculography. The muscle sympathetic nerve activity (MSNA) was recorded directly from the bilateral tibial nerves by using microneurographic double recording technique. Caloric vestibular stimulation was loaded by alternate irrigation with 50 ml of cold (10 degrees C) water and 50 ml of hot (44 degrees C) water into the left and right external meatus. After cold water irrigation, two MSNA response peaks were elicited, respectively, before and after the maximum slow phase velocity (SPV) of nystagmus. The first peak of the MSNA enhancement was caused by non-specific factors because its time course coincided with that in cold pressor test with immersion of the subject's hand in ice/water (4 degrees C). Transient suppression of MSNA after cold water irrigation in the period of maximum SPV of nystagmus was observed by cross correlogram analysis between the SPV of the nystagmus and MSNA. After hot water irrigation, only one MSNA response peak was elicited after the period of strong nystagmus. The second peak of MSNA enhancement evoked by cold irrigation (379.4 +/- 221.8%, with the control value set as 100%, mean +/- SE) was significantly higher than that evoked by hot irrigation (243.0 +/- 14.5%). The degree of MSNA enhancement by either cold (the second peak) or hot stimulation was proportional to the maximum SPV of the nystagmus. There was no significant difference between the MSNA responses ipsilateral to and contralateral to the irrigated side. In conclusion, the caloric vestibular stimulation can influence the bilateral sympathetic outflow to muscle in humans. The degree of MSNA enhancement is proportional to the magnitude of vestibular excitement indicated by maximum slow phase velocity of the nystagmus.

Adult↗

BRCA1 proteins are transported to the nucleus in the absence of serum and splice variants BRCA1a, BRCA1b are tyrosine phosphoproteins that associate with E2F, cyclins and cyclin dependent kinases.

BRCA1, a familial breast and ovarian cancer susceptibility gene encodes nuclear phosphoproteins that function as tumor suppressors in human breast cancer cells. Previously, we have shown that overexpression of a BRCA1 splice variant BRCA1a accelerates apoptosis in human breast cancer cells. In an attempt to determine whether the subcellular localization of BRCA1 is cell cycle regulated, we have studied the subcellular distribution of BRCA1 in asynchronous and growth arrested normal, breast and ovarian cancer cells using different BRCA1 antibodies by immunofluorescence and immunohistochemical staining. Upon serum starvation of NIH3T3, some breast and ovarian cancer cells, most of the BRCA1 protein redistributed to the nucleus revealing a new type of regulation that may modulate the activity of BRCA1 gene. We have also characterized two new variant BRCA1 proteins (BRCA1a/p110 and BRCA1b/ p100) which are phosphoproteins containing phosphotyrosine. Immunofluorescence and Western blotting analysis indicate cytoplasmic and nuclear localization of BRCA1a and BRCA1b proteins. To elucidate the biological function of BRCA1, we created a bacterial fusion protein of glutathione-transferase (GST) and BRCA1 zinc finger domain and detected two cellular proteins with molecular weights of approximately 32 and 65 kD, one of which contains phosphotyrosine designated p32 and p65 BRCA1 interacting proteins (BIP) that specifically interact with BRCA1. Western blot analysis of BIP with cyclins/CDKs and E2F antisera indicated association with cdc2, cdk2, cdk4, cyclin B, cyclin D, cyclin A and E2F-4 but not with cdk3, cdk5, cdk6, E2F-1, E2F-2, E2F-3, E2F-5 and cyclin E. Furthermore, we have also demonstrated a direct interaction of in vitro translated BRCA1a and BRCA1b proteins with recombinant cyclin A, cyclin B1, cyclin D1, cdc2, cdk2 and E2F fusion proteins in vitro. Taken together these results seem to suggest that BRCA1 could be an important negative regulator of cell cycle that functions through interaction with E2F transcriptional factors and phosphorylation by cyclins/cdk complexes with the zinc ring finger functioning as a major protein-protein interaction domain. If the interactions we observe in vitro is also seen in vivo then it may be possible that lack or impaired binding of the disrupted BRCA1 proteins to E2F, cyclins/CDKs in patients with mutations in the zinc finger domain could deprive the cell of an important mechanism for braking cell proliferation leading to the development of breast and ovarian cancers.

3T3 Cells↗

Phenotypes and invariant alpha beta TCR expression of peripheral V alpha 14+ NK T cells.

A novel subset of peripheral T cells, peripheral NK T cells, is found to be a major population comprising 5% of splenic T and 40% of bone marrow T cells. The majority of peripheral NK T cells are characterized by the expression of an invariant TCR-alpha encoded by V alpha 14/J alpha 281 with a one nucleotide N region. Moreover, a specific reduction of V alpha 14+ NK T cells has been demonstrated to be tightly associated with various autoimmune diseases, indicating their decisive role in autoimmune disease development. In this study, we investigated the phenotypes of peripheral V alpha 14+ NK T cells and their TCR-beta repertoire. Peripheral V alpha 14+ NK T cells, comprise two populations, i.e., small and large sized cells, at an equal frequency, belonged to the CD4- CD8- fraction, and are heat stable antigen(bright), macrophage-1bright, B220bright, CD45RBdim, and Mel-14dim, but CD5-, distinct from thymic NK T cells. TCR-beta analysis clearly showed that peripheral V alpha 14+ NK T cells utilized two to three dominant invariant TCR-beta, such as V beta 8.2 D beta J beta 2.5/V beta 7 D beta J beta 2.1 in the spleen and liver, V beta 8.2 D beta J beta 2.5/V beta 8.3 D beta J beta 2.2/V beta 7 D beta J beta 2.6 in the bone marrow, and V beta 7 D beta J beta 2.1/V beta 3 D beta J beta 1.2 in intestinal intraepithelial lymphocytes. Judging from the unusual surface phenotypes, such as heat stable antigen, macrophage-1, B220, CD45RBdim, and Mel-14dim, which are known to be T cell activation markers, peripheral V alpha 14+ NK T cells may always be activated under physiologic conditions, resulting in the oligoclonal expansion of V alpha 14+ NK T cells with different invariant TCR-beta in different peripheral organs. The unique features of V alpha 14+ NK T cells are discussed.

Amino Acid Sequence↗

Epidemiological and clinical studies on an outbreak of trichinosis in central China.

An outbreak of trichinosis occurred in the city of Zhengzhou, central China, between December 1995 and February 1996, affecting 85 of the administrative units into which the city is split. Of 297 subjects from eight of the affected units, 54% were seropositive for Trichinella and 41% had symptoms consistent with acute trichinosis. Of the 490 subjects who had eaten at one particular dumpling restaurant 1-5 weeks before the outbreak and who were traced, 291 (59%) were seropositive and 212 (43%) had been or were ill. MOst of the infections were in manual workers, cadres and merchants aged 20-49 years. Most of those who had been infected failed to develop gastro-intestinal symptoms or a cutaneous rash. Eyelid oedema was only seen in the early stages of the infection, the main clinical manifestations being fever of long duration of tiredness. Surprisingly, six cases had no marked symptoms after repeated infection. Eosinophilia (eosinophils > 7% of leucocytes) was noted in 71 (55%) of the 130 cases in which blood cells were counted. When 212 sera were tested for antibodies to Trichinella, seropositivities were found to increase from 89.1% (IFAT) of 87.7% (microprecipitation test) at presentation to 100% (both tests) 1 week after treatment with albendazole. All those treated were cured. The outbreak was one of the most extensive, single-source outbreaks ever recorded in China, probably with > 600 infections and > 300 clinical cases. The entire episode was attributed to the ingestion of undercooked pork dumplings at one restaurant.

Adolescent↗

Separation of gating properties from permeation and block in mslo large conductance Ca-activated K+ channels.

In this and the following paper we have examined the kinetic and steady-state properties of macroscopic mslo Ca-activated K+ currents in order to interpret these currents in terms of the gating behavior of the mslo channel. To do so, however, it was necessary to first find conditions by which we could separate the effects that changes in Ca2+ concentration or membrane voltage have on channel permeation from the effects these stimuli have on channel gating. In this study we investigate three phenomena which are unrelated to gating but are manifest in macroscopic current records: a saturation of single channel current at high voltage, a rapid voltage-dependent Ca2+ block, and a slow voltage-dependent Ba2+ block. Where possible methods are described by which these phenomena can be separated from the effects that changes in Ca2+ concentration and membrane voltage have on channel gating. Where this is not possible, some assessment of the impact these effects have on gating parameters determined from macroscopic current measurements is provided. We have also found that without considering the effects of Ca2+ and voltage on channel permeation and block, macroscopic current measurements suggest that mslo channels do not reach the same maximum open probability at all Ca2+ concentrations. Taking into account permeation and blocking effects, however, we find that this is not the case. The maximum open probability of the mslo channel is the same or very similar over a Ca2+ concentration range spanning three orders of magnitude indicating that over this range the internal Ca2+ concentration does not limit the ability of the channel to be activated by voltage.

Animals↗

Intrinsic voltage dependence and Ca2+ regulation of mslo large conductance Ca-activated K+ channels.

The kinetic and steady-state properties of macroscopic mslo Ca-activated K+ currents were studied in excised patches from Xenopus oocytes. In response to voltage steps, the timecourse of both activation and deactivation, but for a brief delay in activation, could be approximated by a single exponential function over a wide range of voltages and internal Ca2+ concentrations ([Ca]i). Activation rates increased with voltage and with [Ca]i, and approached saturation at high [Ca]i. Deactivation rates generally decreased with [Ca]i and voltage, and approached saturation at high [Ca]i. Plots of the macroscopic conductance as a function of voltage (G-V) and the time constant of activation and deactivation shifted leftward along the voltage axis with increasing [Ca]i. G-V relations could be approximated by a Boltzmann function with an equivalent gating charge which ranged between 1.1 and 1.8 e as [Ca]i varied between 0.84 and 1,000 microM. Hill analysis indicates that at least three Ca2+ binding sites can contribute to channel activation. Three lines of evidence indicate that there is at least one voltage-dependent unimolecular conformational change associated with mslo gating that is separate from Ca2+ binding. (a) The position of the mslo G-V relation does not vary logarithmically with [Ca]i. (b) The macroscopic rate constant of activation approaches saturation at high [Ca]i but remains voltage dependent. (c) With strong depolarizations mslo currents can be nearly maximally activated without binding Ca2+. These results can be understood in terms of a channel which must undergo a central voltage-dependent rate limiting conformational change in order to move from closed to open, with rapid Ca2+ binding to both open and closed states modulating this central step.

Animals↗

Allosteric gating of a large conductance Ca-activated K+ channel.

Large-conductance Ca-activated potassium channels (BK channels) are uniquely sensitive to both membrane potential and intracellular Ca2+. Recent work has demonstrated that in the gating of these channels there are voltage-sensitive steps that are separate from Ca2+ binding steps. Based on this result and the macroscopic steady state and kinetic properties of the cloned BK channel mslo, we have recently proposed a general kinetic scheme to describe the interaction between voltage and Ca2+ in the gating of the mslo channel (Cui, J., D.H. Cox, and R.W. Aldrich. 1997. J. Gen. Physiol. In press.). This scheme supposes that the channel exists in two main conformations, closed and open. The conformational change between closed and open is voltage dependent. Ca2+ binds to both the closed and open conformations, but on average binds more tightly to the open conformation and thereby promotes channel opening. Here we describe the basic properties of models of this form and test their ability to mimic mslo macroscopic steady state and kinetic behavior. The simplest form of this scheme corresponds to a voltage-dependent version of the Monod-Wyman-Changeux (MWC) model of allosteric proteins. The success of voltage-dependent MWC models in describing many aspects of mslo gating suggests that these channels may share a common molecular mechanism with other allosteric proteins whose behaviors have been modeled using the MWC formalism. We also demonstrate how this scheme can arise as a simplification of a more complex scheme that is based on the premise that the channel is a homotetramer with a single Ca2+ binding site and a single voltage sensor in each subunit. Aspects of the mslo data not well fitted by the simplified scheme will likely be better accounted for by this more general scheme. The kinetic schemes discussed in this paper may be useful in interpreting the effects of BK channel modifications or mutations.

Animals↗

[Volume loading experiment in dogs with large area infarction of right and left ventricles].

In order to study volume loading effect on large area myocardial infarction (MI) in right and left ventricles, large area MI in both ventricles and cardiogenic shock in 12 dogs were induced by occluding coronary arteries. Left ventricular systolic pressure (LVSP) and +/- dp/dt max. dropped markedly by 54%, 51% and 47% respectively, whereas right ventricular systolic pressure (RVSP) and +/- dp/dt max. fell by 9%, 25% and 27% respectively. The condition was obviously worse by rapid volume loading (dextran, 30 ml/kg, i.v. in 20 min.) in group I (n = 6), leading to increased retrograde beat of right ventricle, further decrease of +/- dp/dt max. in both ventricles, significant increase of right atrial pressure (RAP) and left ventricular and diastolic pressure (LEVDP) (2.9 +/- 0.2 kPa, P < 0.01 and 5.0 +/- 0.3 kPa, P < 0.001, respectively), and even ventricular fibrillation. Shock was reversed by combined treatment of dopamine (10 micrograms/kg.min) and glyceryl trinitrate (1 microgram/kg.min) in group II (n = 6) in 30 min, showing evident increase of arterial pressure, cardiac output, LVSP and +/- dp/dt max. without rise in RAP and LVEDP.

Animals↗

[Phenylethanoid glucosides from flos Buddlejae].

Four phenylethanoid glucosides were isolated from the flower of Buddleja officinalis. On the basis of specteral data, they were identified as salidroside(1), verbascoside(2), isoverbascoside(3) and echinacoside(4). Compounds 1, 3 and 4 were obtained from the plant for the first time. Compound 2 showed antibacterial and anticancer activities.

Drugs, Chinese Herbal↗

Sympathetic nerve response to microgravity induced by parabolic flight.

The aim of this study was to clarify how muscle sympathetic nerve activity (MSNA) in humans, which plays an important role in blood pressure control against gravity, is altered under microgravity conditions. Subjects were seated in a jet aircraft with their legs extended. MSNA was recorded microneurographically from the tibial nerve of the sitting subjects with simultaneous monitoring of electrocardiogram, blood pressure, respiration, and intrathoracic blood volume during parabolic flights. In the Air Force training area, the aircraft made parabolas up to 10 times. At the entry to microgravity, intrathoracic blood volume increased, systemic blood pressure was elevated, and MSNA was suppressed. However, this MSNA suppression lasted only 10-15 sec, and then followed by an enhancement to the end of the parabolas. We conclude that MSNA is suppressed at the onset of microgravity during parabolic flight in response to loading of the cardiopulmonary volume receptor due to a cephalad body fluid shift. However, this MSNA suppression is transient during such dynamic gravitational changes as those induced by parabolic flight, probably modulated by arterial baroreceptors.

Adult↗

[A novel immune system].

We found a novel lymphoid cell lineage, V alpha 14 NKT cell, which is characterized by 1) the expression of both NK1.1 (NK receptor) and an invariant TCR encoded by V alpha 14 and J alpha 281 gene segments; 2) the expression of unusual phenotypes, such as NK1.1+, B220+, Mac-1+, HSA+, CD44+, CD45Rlow and MEL-14low; and 3) the extrathymic development: V alpha 14 NKT cells appear at d9.5 of gestation before thymus development. Moreover, the deletion of the invariant V alpha 14 TCR gene expression caused the lack of NKT cells in vivo, while transgene of the invariant V alpha 14 V beta 8 TCR in the RAG-deficient background resulted in the generation of only V alpha 14 NKT cells without other lymphoid cells. These results indicate the essential requirement of invariant V alpha 14 TCR for the development of NKT cells. Recent studies clearly show that V alpha 14 NKT cells, but not NK cells or T cells are the primary target of IL-12 in the IL-12-mediated tumor rejection.

Animals↗