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Biomedical subjects

L Liu

Publications and source records attributed to L Liu.

At least 775 records · Page 43Linked to original sources
PubMed1997

Crucial role of interleukin-10/interleukin-12 balance in the regulation of the type 2 T helper cytokine response in reactive arthritis.

OBJECTIVE: To investigate whether a predominant type 1 T helper (Th1) or Th2 cytokine pattern is present in the joints of patients with reactive arthritis (ReA), and whether the cytokine pattern can be modulated by cytokines or anticytokines. METHODS: Eleven patients with ReA following infection with either Chlamydia trachomatis, Yersinia enterocolitica, or Salmonella enteritidis were investigated for the presence of Th1/Th2 cytokines in the joints. Release of the bacteria-specific cytokines interferon-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), interleukin-10 (IL-10), and IL-4 was measured in synovial fluid mononuclear cells (SFMC) using enzyme-linked immunosorbent assay and polymerase chain reaction. In the synovial membrane, secretion of IFN gamma and IL-4 was determined by immunohistologic analysis. Cytokine regulation was studied by adding cytokines and anticytokines to the cultures. RESULTS: Upon stimulation with specific bacteria, SFMC secreted low amounts of IFN gamma and TNF alpha, but high amounts of IL-10. IL-10 was responsible for the suppression of IFN gamma and TNF alpha, as judged by the effect of adding either anti-IL-10 antibodies or exogenous IL-10 to these cultures. The addition of neutralizing anti-IL-12 to the cultures completely abolished the effects of anti-IL-10, suggesting that inhibition of the Th1-like cytokines by IL-10 is mediated through suppression of IL-12 synthesis. Exogenous IL-12 clearly enhanced IFN gamma and TNF alpha secretion. In the synovial membrane, a higher number of cells were positive for the Th2 cytokine IL-4, compared with the amount of IFN gamma-secreting cells. CONCLUSION: These data indicate that a Th2 cytokine pattern predominates in the joints of patients with ReA. Since Th1 cytokines are necessary for the elimination of ReA-associated bacteria, Th2 cytokines might contribute to bacterial persistence in the joint. Therefore, the IL-10/IL-12 balance appears to be crucial for regulation of the cytokine pattern in the joints of patients with ReA.

Adolescent↗
PubMed1997

Differential association of phosphatases with hematopoietic co-receptors bearing immunoreceptor tyrosine-based inhibition motifs.

A novel family of inhibitory co-receptors has been recently defined according to the presence in their intracytoplasmic domain of immunoreceptor tyrosine-based inhibition motifs (ITIM). In particular, this family includes a low-affinity receptor for IgG, Fc gammaRIIB, which is widely expressed on hematopoietic cells, as well as killer cell inhibitory receptors (KIR) for major histocompatibility complex (MHC) class I proteins, expressed on both T and natural killer (NK) lymphocytes. Fc gammaRIIB and KIR inhibitory function depends upon the tyrosine phosphorylation of their respective ITIM. Phosphorylated Fc gammaRIIB and KIR ITIM bind the tandem SH2 tyrosine phosphatases, SHP-1 and SHP-2. Recently, Fc gammaRIIB has been shown to associate with a polyphosphate inositol 5-phosphatase, SHIP, which appears to be involved in its inhibitory function. Using cell lysate adsorption to phosphorylated ITIM peptides and surface plasmon resonance, we demonstrate here that, in contrast to Fc gammaRIIB, KIR (CD158b: p58.2) do not bind to SHIP, and only recruit SHP-1 and SHP-2. In addition, we show that point mutation of the amino acid residue in position tyrosine-2 of Fc gammaRIIB and KIR ITIM abolihes their binding to SHP-1 and SHP-2, but leaves intact the association of SHIP with Fc gammaRIIB ITIM. These data contribute to the structural definition of ITIM and document a differential recruitment of phosphatases by distinct ITIM. These findings also reveal that diverse strategies of inhibition are used by distinct members of the ITIM-bearing co-receptor family.

Amino Acid Sequence↗
PubMed1997

Desensitization of the fMLP-induced NADPH-oxidase response in human neutrophils is lacking in okadaic acid-treated cells.

The chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP) interacts with neutrophils, generating signals that induce activation of the superoxide anion/hydrogen peroxide-producing NADPH-oxidase. Low temperature binding of fMLP to its neutrophil surface receptors is associated with a desensitization of the cells with respect to activation of the oxidase. Other stimuli can still activate the oxidase (in fact even induce a primed response), indicating that the observed phenomenon is stimulus specific and could not be accounted for by an effect on the oxidase itself. Furthermore, no desensitization is obtained in the presence of cytochalasin B, suggesting that the cytoskeleton is involved in the process leading to desensitization. Okadaic acid is a toxin produced by dinoflagellates and exerts its effects by an inhibition of cellular phosphatases. To investigate the role of phosphorylation/dephosphorylation events in the desensitization process we used okadaic acid as a scientific tool. We show that neutrophils treated with okadaic acid are primed with respect to the fMLP-induced production of superoxide anion, and that no desensitization is obtained in toxin-treated cells. Because the recovery of ligand-receptor complexes in a Triton X-100-insoluble fraction is very low in the cells treated with okadaic acid, we suggest that protein dephosphorylation is required to obtain binding to the cytoskeleton of occupied fMLP receptors; binding of the occupied receptors to the cell cytoskeleton being the mechanism behind desensitization.

Adult↗
PubMed1997

Phenylacetate and phenylbutyrate as novel, nontoxic differentiation inducers.

Phenylacetate and analogs represent a new class of pleiotropic growth regulators that alter tumor cell biology by affecting gene expression at both the transcriptional and post transcriptional levels. Based on these findings, NaPA and NaPB entered clinical trials at the National Cancer Institute. Ongoing phase I studies with NaPA, involving adults with prostate and brain cancer, have confirmed that therapeutic levels can be achieved with no significant toxicities, and provide preliminary evidence for benefit to patients with advanced disease (Thibault et al., submitted).

Adult↗
PubMed1997

Gadolinium-enhanced magnetic resonance angiography of the pelvis in patients with erectile impotence.

This study evaluated the potential of contrast-enhanced digital-subtraction magnetic resonance angiography (CE-DS-MRA) for noninvasive angiographic delineation of the arterial supply of the penis in patients with erectile dysfunction. After induction of an erection with prostaglandin E, a three-dimensional fast imaging with steady-state precision (FISP) sequence with TE of 1.8-2 milliseconds, TR of 4.4-5 milliseconds, and flip angle of 40 degrees-60 degrees was used to obtain high-resolution angiograms of the pelvis and penis during the injection of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) 0.3 mmol/kg body weight, within 30-50 seconds. DS maximum intensity projections (MIPs) and multiplanar reconstructions (MPRs) were compared with clinical work-up and directional Doppler ultrasound in 11 patients. In all 11 patients (100%), the arterial supply of the penis could be delineated from the aortic bifurcation via the iliac and internal pudendal arteries to the dorsal and deep penile arteries. Of the 22 internal pudendal arteries, 6 (27%) were occluded on CE-DS-MRA and 5 (23%) had stenoses, of which 4 (18%) were greater than 50%. In 7 patients (64%) good correlation between CE-DS-MRA and clinical findings and/or Doppler ultrasound was found; in 2 patients (18%), the correlation was moderate, and in 2 patients (18%) results were discrepant. In 6 patients (55%), MRA provided additional information to the clinical and Doppler ultrasound work-up. CE-DS-MRA can delineate small vessels such as the internal pudendal and penile arteries and thus has the potential to become a noninvasive angiography method in the work-up of erectile impotence.

Arteries↗
PubMed1997

Characterisation of pre- and post-synaptic alpha-adrenoceptors in modulation of the rat ileum longitudinal and circular muscle activities.

Previous study has shown that alpha2D-adrenoceptors are involved in modulation of peristalsis in the rat ileum. The aim of the present study was to determine the tissue location of alpha-adrenoceptors in the rat ileum by using a recently devised method. The pre-synaptic alpha-adrenoceptors were characterised by measuring the potencies of agonists to inhibit transmurally-evoked (1 ms pulses, 10 Hz, 8-10 s trains) contractions of the longitudinal and circular muscles and the affinities of antagonists. Post synaptic alpha-adrenoceptors were identified by screening agonists and antagonists in carbachol-contracted tissues. In the circular muscle the order of potencies for inhibiting transmurally-induced contraction was: clonidine > or = oxymetazoline > or = UK 14,304 > or = guanfacine > talipexole > phenylephrine > azepexole. The potency ratios relative to clonidine correlated to those previously derived using the rat ileum peristaltic reflex preparation. Most of the alpha-adrenoceptor agonists, however, caused only small inhibitions of the longitudinal muscle contraction in response to transmural stimulation, except phenylephrine and azepexole. RX 821002, yohimbine, rauwolscine, BRL 44408, phentolamine, idazoxan, ARC 239, and prazosin inhibited the effect of clonidine on the circular muscle response with apparent pK(B) values best correlated with pK(B) or pKi values derived from the rat ileum peristaltic reflex preparation and other tissues known to have the alpha2D-subtype. The rank order of potencies at inhibiting carbachol-induced responses of both muscle layers was: phenylephrine > or = oxymetazoline > clonidine > or = talipexole > azepexole >> guanfacine. UK 14,304 was inactive up to 10 microM. The EC50 value of each agonist on the longitudinal muscle was not significantly different to the corresponding value on the circular muscle. Prazosin was more potent than yohimbine at inhibiting the relaxant effect of phenylephrine in both muscle layers of carbachol-contracted tissues. It is concluded that the recently identified alpha2D-adrenoceptors of the rat ileum are located on cholinergic neurons controlling circular muscle contraction. The study also demonstrated the presence of postsynaptic alpha1-adrenoceptors involved in mediating relaxation in both muscle layers.

Adrenergic alpha-Agonists↗
PubMed1997

The expression of tumor necrosis factor-alpha in the rat brain after fluid percussive injury.

To investigate the role of tumor necrosis factor-alpha (TNF alpha) after traumatic head injury in rats, moderate brain injury of 1000 mmHg was generated by an original fluid percussion injury device. TNF alpha levels in cerebrospinal fluid (CSF) gradually increased during the first 1 h, rose to a maximal elevation at 3 h and 6 h and returned to basal values by 24 h. Horseradish peroxidase tracer experiments revealed that primary microvascular damage appeared as early as 15 min after impact, but rapidly recovered and 1 h after impact secondary microvascular damage occurred in the hippocampus and parasagittal cortex. By immunoelectron microscopy, TNF alpha reactions were detected in the lysosomes of microglia accumulated at the impact site of the cortex 30 min after impact, and 1 h after impact these reactions were mainly detected at the glial cells (such as microglia and astrocytes) in the hippocampus and parasagittal cortex. Therefore the delayed microvascular damage observed in sites remote from the impact may be induced by TNF alpha which is synthesized mainly by glial cells. The present study suggests that TNF alpha conveyed from the microglial cells is one co-factor contributing to the fluid percussive brain edema formation after moderate brain injury.

Animals↗
PubMed1997

Recurrence patterns with concurrent platinum-based chemotherapy and accelerated hyperfractionated radiotherapy in stage III and IV head and neck cancer patients.

BACKGROUND: Stage III and IV squamous cell cancers of the head and neck are often unresectable at presentation and are associated with poor disease-free and overall survival rates. A phase II study using concurrent cisplatin and radiotherapy in advanced head and neck cancer indicated impressive local-regional control and survival with organ preservation. METHODS: A multicentered phase II study was undertaken consisting of 1.8 Gy fraction radiotherapy for 2 weeks followed by 1.2 Gy BID hyperfractionation to 46.8 Gy. Continuous infusion cisplatin 20 mg/m2 was given on days 1 through 4 and 22 through 25. Biopsy of the primary tumor was done at this point, and patients with clinical and pathologic complete response continued with hyperfractionated radiotherapy to 75.6 Gy plus simultaneous carboplatin 25 mg/m2 BID for 12 consecutive days. Residual disease at 46.8 Gy required curative surgery. RESULTS: Seventy-four patients entered the study, and 73 completed their treatment. Twenty were stage III and 54 were stage IV. Fifty patients had involved regional lymph nodes. Treatment was well tolerated with only one grade IV hematologic toxicity. At 46.8 Gy, biopsy revealed a complete response in 75% of the primary sites and 47% of the nodes. Only 12 patients required resection of the primary lesion. At 4 years (median follow-up is 26 months), 29 patients have recurred. CONCLUSIONS: Accelerated hyperfractionated radiotherapy with concurrent chemotherapy in stage III and IV head and neck cancer yields excellent local-regional control with organ preservation. This protocol is intensive, and some patients have distant failures.

Antineoplastic Agents↗
PubMed1997

Mice lacking transforming growth factor alpha have an increased susceptibility to dextran sulfate-induced colitis.

BACKGROUND & AIMS: There is indirect evidence that transforming growth factor alpha (TGF-alpha) is an important mediator of mucosal defense and repair. TGF-alpha knockout mice and TGF-alpha-deficient mice (wa-1) provide novel approaches to evaluate the role of TGF-alpha in preserving the integrity of the colon. METHODS: Colitis was induced by oral administration of dextran sodium sulfate (DSS, 5 g/dL) to knockout mice, their genetic controls (GC), wa-1 mice, and BALB/c mice. TGF-alpha was also administered intraperitoneally to wa-1 mice to evaluate the effect of exogenous TGF-alpha in DSS colitis. RESULTS: In response to DSS, nearly 60% of the entire colonic mucosa was destroyed in knockout and wa-1 mice, compared with 22% in GC mice and 16% in BALB/ c mice. Body weight loss was doubled in knockout (28%) and wa-1 mice (23%) compared with GC (11%) and Balb/c mice (12%). TGF-alpha application to wa-1 mice reduced the severity of mucosal injury by almost 70% compared with controls. CONCLUSIONS: The marked susceptibility of TGF-alpha knockout and wa-1 mice to DSS and the obvious amelioration of the colonic injury by exogenous TGF-alpha application in wa-1 mice suggest that TGF-alpha is a mediator of protection and/or healing mechanisms in the colon.

Animals↗
PubMed1997

Nutritional effects on operant visual learning in Drosophila melanogaster.

The nutritional effects on operant visual learning behavior were investigated in a flight simulator. Operant visual learning and memory formation were normal in Drosophila (S-flies) reared on standard medium, but absent in flies (P-flies) raised on Peking medium. S- and P-flies were transferred to the alternative medium soon after hatching and their progeny was also raised on corresponding medium for several generations. respectively. S-flies transferred showed significantly reduced learning acquisition and 20 min memory retention, and operant visual learning along with memory formation was abolished in their progeny within three generations. Transferred P-flies recovered slowly their learning acquisition and memory formation to normal levels within five generations. Further studies suggested that low protein and minerals or high carbohydrate contents in Peking medium might be related to abnormal performance of P-flies. These results confirm the feasibility of affecting learning behavior by dietary regimens and developing an insect model of maternal malnutrition for pre- or post-natal malnutrition in Drosophila.

Animal Feed↗
PubMed1997

Binocular matching of dissimilar features in phantom stereopsis.

Previously we have demonstrated that quantitative depth perception can be elicited from a stereogram that lacks contrast defined binocular corresponding elements (phantom stereopsis). In this report, we use computer simulation to demonstrate that it is biologically plausible for some known binocular cortical cell types to combine non-conventional matching features. Therefore, binocular matching processes based on the responses of these cells could be a conventional one, namely, looking for similar response patterns in the two eyes. While at cell types we simulated gave identical disparity outputs to the conventional stereogram, they responded differently to the phantom stereogram. Processes other than low-level disparity detectors may have to be invoked in order to achieve a unique depth solution.

Computer Simulation↗
PubMed1997

Drug disruption of short-term memory in Drosophila melanogaster.

Recent work on operant visual learning and memory in Drosophila has suggested at least three distinct memory phases. Trying to disrupt memory pharmacologically, we fed flies with ouabain or the depolarizing drugs potassium chloride (KCl), lithium chloride (LiCl) and monosodium glutamate for some specific time before training. The depolarizing drugs abolished memory very soon after training. Ouabain exerted no effect on memory within the first 20 min but abolished it more than 30 min after training. These drugs had no diminishing effects on the visual discrimination and behavioral performance of the flies during training. This result suggests that memory disruption may not be induced by nonspecific effects of the drugs. In addition, reversal training of the KCl-fed flies indicates that KCl appears not to impair the retrieval mechanism of flies. These results suggest that the specific disruptive effects of the drugs on memory formation and the existence of a short-term memory phase, are susceptible to disruption of the depolarizing drugs but unaffected by ouabain.

Animals↗
PubMed1997

Inactivation of rotavirus by new polymeric water disinfectants.

Two new insoluble polymeric materials were evaluated for their efficacies in inactivating rotavirus in flowing water in a biocidal filter application. The two polymers are N-chloro and N-bromo derivatives of a poly-styrene hydantoin prepared from commercial poly-styrene. The studies were conducted for rotavirus in halogen demand-free water at pH 7.0, 25 degrees C and Environmental Protection Agency (EPA) Test Water no. 2 at pH 9.0, 4 degrees C which contained heavy halogen demand. The range of flow rates studied was 0.16-1.22 ml s-1 corresponding to contact times in the range of 4-24 s. Both of the polymers were effective in inactivating rotavirus, the N-bromo derivative providing a 4-6 log reduction under the test conditions. The materials may be useful as supplemental filters for hand-held water purification units.

Disinfectants↗
PubMed1997

Response of glial cells and activation of complement following motorneuron degeneration induced by toxic ricin.

Motor nerve transection in adult rats induce a series of metabolic and structural changes in the injured neurons as well as in surrounding glial cells; however, without substantial neuronal degeneration. In the present study we found, in contrast with axotomy, a massive neuronal death in the ipsilateral hypoglossal nucleus following injection of toxic ricin (RCA) into the hypoglossal nerve, which is in line with previous observations. Injection of RCA enables examination of the glial reaction in a situation where neuronal degeneration is profound, which has been the approach in the present study. We found an increase in OX42-, GFAP-, and transferrin-immunoreactivity in microglial, astroglial, and oligodendroglial cells respectively, in the ipsilateral hypoglossal nucleus three to seven days following injection of toxic ricin in the hypoglossal nerve. Proliferation was found in astrocytes as well as in microglial cells, as shown by uptake of bromodeoxyuridine. In addition, the complement cascade was activated locally in the ipsilateral hypoglossal nucleus, as demonstrated by immunohistochemical detection of complement components C3d and C9. Complement activation may serve several effects in the glial-neuronal interactions. Stimulation of phagocytosis by reactive microglia is probably the most important one. Furthermore, the degenerative neuronal somata showed increased immunoreactivity for clusterin, which is a known complement inhibitor, but a decrease in clusterin-mRNA. In conclusion, the glial cell response was in several aspects principally different following massive motorneuron degeneration induced by toxic ricin in comparison to previous findings reported after axotomy.

Animals↗
PubMed1997

Structural organization of the human vesicular monoamine transporter type-2 gene and promoter analysis using the jelly fish green fluorescent protein as a reporter.

The genomic structure of a human vesicle monoamine transporter, type-2 (hVMAT2) was determined from two overlapping cosmids, phVMAT2-cos1 and phVMT2-cos2, spanning more than 35 kb. The hVMAT2 open reading frame is encoded by 16 exons, with translation initiation and termination in exon 2 and exon 16, respectively. Several potential binding sites for transcriptional regulatory factors, including a cAMP response element (CRE) were identified in the 5'-upstream region of the gene. A promoter construct using the jellyfish green fluorescent protein (GFP) as reporter has been made and transfected into the human neuroblastoma cell line, SHSY-5Y. The cellular expression of the GFP was readily detected by fluorescence microscopy and cells expressing GFP could be sorted using a fluorescence-activated cell sorter (FACS), allowing the level of GFP expression in transfected SHSY-5Y cells to be quickly and reliably determined.

Amino Acid Sequence↗
PubMed1997

Factors affecting electrical activation of porcine oocyte matured in vitro.

This work was undertaken to improve conditions for in vitro maturation and activation of porcine oocytes. Experiments were designed to compare: (i) electrical pulse frequency, (ii) methods of oocyte preparation, (iii) maturation conditions, and (iv) electrical poration medium on development. Oocytes were harvested by follicle dissection or aspiration, co-cultured with follicle shells in M199 based medium with or without media changes at 38.5 degrees C in 5% CO2 under non-static conditions for 48 h and electroactivated using single or multiple pulses (current strength 1.0 kV/cm for 50 microseconds in 0.28 M inositol or mannitol based media with 10 mM histidine) at different time intervals. The results showed: (i) neither the pulse frequency nor the pulse interval influenced rates of pronuclear formation but multiple pulse activation (3 pulses at 5 min intervals) induced a higher incidence of development and progression through the 4-cell block in contrast to one pulse activation; (ii) both the rate of nuclear maturation (88.6% vs. 77.6%) and post-activation cleavage (89.8% vs. 67.4%) were higher (P < 0.05) when oocytes were collected by follicle dissection rather than by aspiration; (iii) while changing to a hormone-free medium at 24 h was without effect on maturation (91.9% vs. 91.7%), rate of cleavage (81.6% vs. 72.3%, P < 0.05) at 24 h was enhanced by the medium change; and (iv) oocytes activated with 3 pulses 5 min apart in mannitol based medium at 48-49 h and at 53-54 h formed pronuclei at a comparable rate but subsequent parthenogenetic development was higher in the older eggs. By contrast, inositol-based medium supported development of young and old eggs equally well. Calcium and magnesium ions are, however, necessary in both mannitol and inositol media for activation of porcine oocytes matured in vitro. The present results suggest that optimal parthenogenetic activation and early development of IVM pig oocytes could be obtained if oocytes are harvested by dissection, cultured for 24 h in hormone-containing medium before being placed in hormone free medium and activated at 48 h in inositol based medium using a three pulse activation system.

Aging↗