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J H Liu

Publications and source records attributed to J H Liu.

At least 145 records · Page 8Linked to original sources
PubMed1998

Dysregulation of CD95/CD95 ligand-apoptotic pathway in CD3(+) large granular lymphocyte leukemia.

CD95 (Fas)-induced apoptosis plays a critical role in the elimination of activated lymphocytes and induction of peripheral tolerance. Defects in CD95/CD95L (Fas-Ligand)-apoptotic pathway have been recognized in autoimmune lymphoproliferative diseases (ALPS) and lpr or gld mice and attributed to CD95 and CD95L gene mutations, respectively. Large granular lymphocyte (LGL) leukemia is a chronic disease characterized by a proliferation of antigen-activated cytotoxic T lymphocytes. Autoimmune features such as hypergammaglobulinemia, rheumatoid factor, and circulating immune complexes are common features in LGL leukemia and ALPS. Therefore, we hypothesize that expansion of leukemic LGL may be secondary to a defective CD95 apoptotic pathway. In this study, we investigated expression of CD95 and CD95L in 11 patients with CD3(+) LGL leukemia and explored the apoptotic response to agonistic CD95 monoclonal antibody (MoAb). We found that leukemic LGL from each patient expressed constitutively high levels of CD95/CD95L, similar to those seen in normal activated T cells. However, cells from 9 of these 11 patients were totally resistant to anti-CD95-induced apoptosis. Similarly, cells were resistant to anti-CD3-MoAb-triggered cell death. Lack of anti-CD95-induced apoptosis was not due to mutations in the CD95 antigen. Leukemic LGL were not intrinsically resistant to CD95-dependent death, because LGL from all but 1 patient underwent apoptosis after phytohemagglutinin/interleukin-2 activation. The patient whose leukemic LGL were intrinsically resistant to CD95 had an aggressive form of LGL leukemia that was resistant to combination chemotherapy. These findings that leukemic LGL are resistant to CD95-dependent apoptosis despite expressing high levels of CD95 are similar to observations made in CD95L transgenic mice. These data suggest that LGL leukemia may be a useful model of dysregulated apoptosis causing human malignancy and autoimmune disease.

Adult↗
PubMed1998

An ether -à-go-go K+ current, Ih-eag, contributes to the hyperpolarization of human fusion-competent myoblasts.

1. Two early signs of human myoblast commitment to fusion are membrane potential hyperpolarization and concomitant expression of a non-inactivating delayed rectifier K+ current, IK(NI). This current closely resembles the outward K+ current elicited by rat ether-à-go-go (r-eag) channels in its range of potential for activation and unitary conductance. 2. It is shown that activation kinetics of IK(NI), like those of r-eag, depend on holding potential and on [Mg2+]o, and that IK(NI), like r-eag, is reversibly inhibited by a rise in [Ca2+]i. 3. Forced expression of an isolated human ether-à-go-go K+ channel (h-eag) cDNA in undifferentiated myoblasts generates single-channel and whole-cell currents with remarkable similarity to IK(NI). 4. h-eag current (Ih-eag) is reversibly inhibited by a rise in [Ca2+]i, and the activation kinetics depend on holding potential and [Mg2+]o. 5. Forced expression of h-eag hyperpolarizes undifferentiated myoblasts from -9 to -50 mV, the threshold for the activation of both Ih-eag and IK(NI). Similarly, the higher the density of IK(NI), the more hyperpolarized the resting potential of fusion-competent myoblasts. 6. It is concluded that h-eag constitutes the channel underlying IK(NI) and that it contributes to the hyperpolarization of fusion-competent myoblasts. To our knowledge, this is the first demonstration of a physiological role for a mammalian eag K+ channel.

Adolescent↗
PubMed1998

Use of fluorescein labelled antibody and fluorescence activated cell sorter for rapid identification of Mycobacterium species.

A fluorescein labelled antibody (Ab)/Fluorescence Activated Cell Sorter (FACS)-based assay was developed for detection of a wide range of mycobacterial species directly from bacterial culture and sputum specimens. The whole process could be completed within 3 hours and had a high specificity and sensitivity for cultured bacteria. The method was also shown to be applicable for direct identification from clinical specimens. This study showed that pretesting of clinical specimens for mycobacteria to the genus level with an antibody to Mycobacterium species offers the routine clinical laboratory a single convenient test for the detection of tuberculous and nontuberculous mycobacteria. Depending on the availability of species-specific antibody, the identification of Mycobacterium to the species level can be achieved.

Antibodies, Bacterial↗
PubMed1998

Cloning of a human ether-a-go-go potassium channel expressed in myoblasts at the onset of fusion.

An early sign of human myoblast commitment to fusion is the expression of a non-inactivating delayed rectifier K+ current, I(K(NI)), and an associated membrane potential hyperpolarization. We have isolated the full-length coding region of a human ether-a-go-go K+ channel (h-eag) from myoblasts undergoing differentiation. The h-eag gene was localized to chromosome 1q32-41, and is expressed as a approximately 9 kb transcript in myogenic cells and in adult brain tissue. Forced expression of h-eag in undifferentiated myoblasts generates a current with remarkable similarity to I(K(NI)) indicating that h-eag constitutes the channel responsible for this current in vivo.

Adolescent↗
PubMed1998

Differential thymic selection outcomes stimulated by focal structural alteration in peptide/major histocompatibility complex ligands.

The T lineage repertoire is shaped by T cell receptor (TCR)-dependent positive and negative thymic selection processes. Using TCR-transgenic (N15tg) beta2-microglobulin-deficient (beta2m-/-) RAG-2(-/-) H-2(b) mice specific for the VSV8 (RGYVYQGL) octapeptide bound to Kb, we identified a single weak agonist peptide variant V4L (L4) inducing phenotypic and functional T cell maturation. The cognate VSV8 peptide, in contrast, triggers negative selection. The crystal structure of L4/Kb was determined and refined to 2.1 A for comparison with the VSV8/Kb structure at similar resolution. Aside from changes on the p4 side chain of L4 and the resulting alteration of the exposed Kb Lys-66 side chain, these two structures are essentially identical. Hence, a given TCR recognizes subtle distinctions between highly related ligands, resulting in dramatically different selection outcomes. Based on these finding and the recent structural elucidation of the N15-VSV8/Kb complex, moreover, it appears that the germ-line Valpha repertoire contributes in a significant way to positive selection.

Amino Acid Sequence↗
PubMed1998

Role of an inward rectifier K+ current and of hyperpolarization in human myoblast fusion.

1. The role of K+ channels and membrane potential in myoblast fusion was evaluated by examining resting membrane potential and timing of expression of K+ currents at three stages of differentiation of human myogenic cells: undifferentiated myoblasts, fusion-competent myoblasts (FCMBs), and freshly formed myotubes. 2. Two K+ currents contribute to a hyperpolarization of myoblasts prior to fusion: IK(NI), a non-inactivating delayed rectifier, and IK(IR), an inward rectifier. 3. IK(NI) density is low in undifferentiated myoblasts, increases in FCMBs and declines in myotubes. On the other hand, IK(IR) is expressed in 28% of the FCMBs and in all myotubes. 4. IK(IR) is reversibly blocked by Ba2+ or Cs+. 5. Cells expressing IK(IR) have resting membrane potentials of -65 mV. A block by Ba2+ or Cs+ induces a depolarization to a voltage determined by IK(NI) (-32 mV). 6. Cs+ and Ba2+ ions reduce myoblast fusion. 7. It is hypothesized that the IK(IR)-mediated hyperpolarization allows FCMBs to recruit Na+, K+ and T-type Ca2+ channels which are present in these cells and would otherwise be inactivated. FCMBs, rendered thereby capable of firing action potentials, could amplify depolarizing signals and may accelerate fusion.

Action Potentials↗
PubMed1998

The structure of immunoglobulin superfamily domains 1 and 2 of MAdCAM-1 reveals novel features important for integrin recognition.

BACKGROUND: Mucosal addressin cell adhesion molecule 1 (MAdCAM-1) is a cell adhesion molecule that is expressed on the endothelium in mucosa, and guides the specific homing of lymphocytes into mucosal tissues. MAdCAM-1 belongs to a subclass of the immunoglobulin superfamily (IgSF), the members of which are ligands for integrins. Human MAdCAM-1 has a unique dual function compared to other members in the same subclass in that it binds both the integrin alpha4beta7, through its two IgSF domains, and a selectin expressed on leukocytes, via carbohydrate sidechains. The structure determination of the two IgSF domains and comparison to the N-terminal two-domain structures of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecules (ICAM-1 and ICAM-2) allow us to assess the molecular basis of the interactions between integrins and their preferred ligands. RESULTS: The crystal structure of a fragment containing the two IgSF domains of human MAdCAM-1 has been determined to 2.2 A resolution. The structure of MAdCAM-1 reveals two separate integrin-recognition motifs. The key integrin-binding residue, Asp42, resides in the CD loop of domain 1; a buried arginine residue (Arg70) plays a critical role in maintaining the conformation of this loop. The second binding site is associated with an unusual long D strand in domain 2. The D and E strands extend beyond the main body of the domain, forming a negatively charged beta ribbon unique to MAdCAM-1. This ribbon is located on the same face as the key aspartate residue in domain 1, consistent with evidence that it is involved in integrin binding. CONCLUSIONS: The structural comparison of MAdCAM-1 to other members of the same IgSF subclass reveals some interesting features. Firstly, MAdCAM-1, like VCAM-1, has the key integrin-binding residue located on the protruding CD loop of domain 1 and binds to an integrin that lacks an I domain. This is in contrast to ICAM-1 and ICAM-2 where the key residue is located at the end of the C strand on a flat surface and which bind to integrins that contain I domains. Secondly, architectural differences in the CD loops of MAdCAM-1 and VCAM-1 cause an 8 A shift in position of the critical aspartate residue, and may partly determine their binding preference for different integrins. Finally, the unusual charge distribution of the two-domain fragment of MAdCAM-1 is predicted to orient the molecule optimally for integrin binding on the top of its long mucin-like stalk.

Amino Acid Sequence↗
PubMed1998

Control of lytic function by mitogen-activated protein kinase/extracellular regulatory kinase 2 (ERK2) in a human natural killer cell line: identification of perforin and granzyme B mobilization by functional ERK2.

The signal pathways that control effector function in human natural killer (NK) cells are little known. In this study, we have identified the critical role of the mitogen-activated protein kinase (MAPK) pathway in NK lysis of tumor cells, and this pathway may involve the mobilization of granule components in NK cells upon interaction with sensitive tumor target cells. Evidence was provided by biological, biochemical, and gene transfection methods. NK cell binding to tumor cells for 5 min was sufficient to maximally activate MAPK/extracellular signal-regulatory kinase 2 (ERK2), demonstrated by its tyrosine phosphorylation and by its ability to function as an efficient kinase for myelin basic protein. MAPK activation was achieved in NK cells only after contact with NK-sensitive but not NK-resistant target cells. In immunocytochemical studies, cytoplasmic perforin and granzyme B were both maximally redirected towards the tumor contact zone within 5 min of NK cell contact with tumor cells. A specific MAPK pathway inhibitor, PD098059, could block not only MAPK activation but also redistribution of perforin/granzyme B in NK cells, which occur upon target ligation. PD098059 also interfered with NK lysis of tumor cells in a 5-h 51Cr-release assay, but had no ability to block NK cell proliferation. Transient transfection studies with wild-type and dominant-negative MAPK/ERK2 genes confirmed the importance of MAPK in NK cell lysis. These results document a pivotal role of MAPK in NK effector function, possibly by its control of movement of lytic granules, and clearly define MAPK involvement in a functional pathway unlinked to cell growth or differentiation.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

A dimeric crystal structure for the N-terminal two domains of intercellular adhesion molecule-1.

The 3.0-A structure of a 190-residue fragment of intercellular adhesion molecule-1 (ICAM-1, CD54) reveals two tandem Ig-superfamily (IgSF) domains. Each of two independent molecules dimerizes identically with a symmetry-related molecule over a hydrophobic interface on the BED sheet of domain 1, in agreement with dimerization of ICAM-1 on the cell surface. The residues that bind to the integrin LFA-1 are well oriented for bivalent binding in the dimer, with the critical Glu-34 residues pointing away from each other on the periphery. Residues that bind to rhinovirus are in the flexible BC and FG loops at the tip of domain 1, and these and the upper half of domain 1 are well exposed in the dimer for docking to virus. By contrast, a residue important for binding to Plasmodium falciparum-infected erythrocytes is in the dimer interface. The presence of A' strands in both domains 1 and 2, conserved hydrogen bonds at domain junctions, and elaborate hydrogen bond networks around the key integrin binding residues in domain 1 make these domains suited to resist tensile forces during adhesive interactions. A subdivision of the intermediate (I) set of IgSF domains is proposed in which domain 1 of ICAM-1 and previously described I set domains belong to the I1 set and domain 2 of ICAM-1, ICAM-2, and vascular cell adhesion molecule-1 belong to the I2 set.

Amino Acid Sequence↗
PubMed1998

Identification of a common docking topology with substantial variation among different TCR-peptide-MHC complexes.

Whether T-cell receptors (TCRs) recognize antigenic peptides bound to major histocompatability complex (MHC) molecules through common or distinct docking modes is currently uncertain. We report the crystal structure of a complex between the murine N15 TCR [1-4] and its peptide-MHC ligand, an octapeptide fragment representing amino acids 52-59 of the vesicular stomatitis virus nuclear capsid protein (VSV8) bound to the murine H-2Kb class I MHC molecule. Comparison of the structure of the N15 TCR-VSV8-H-2Kb complex with the murine 2C TCR-dEV8-H-2Kb [5] and the human A6 TCR-Tax-HLA-A2 [6] complexes revealed a common docking mode, regardless of TCR specificity or species origin, in which the TCR variable Valpha domain overlies the MHC alpha2 helix and the Vbeta domain overlies the MHC alpha1 helix. As a consequence, the complementary determining regions CDR1 and CDR3 of the TCR Valpha and Vbeta domains make the major contacts with the peptide, while the CDR2 loops interact primarily with the MHC. Nonetheless, in terms of the details of the relative orientation and disposition of binding, there is substantial variation in TCR parameters, which we term twist, tilt and shift, and which define the variation of the V module of the TCR relative to the MHC antigen-binding groove.

Animals↗
PubMed1998

Endogenous Candida endophthalmitis after induced abortion.

PURPOSE: To report two young healthy women who developed endogenous Candida endophthalmitis after undergoing surgically induced abortion. METHOD: Case reports. RESULTS: In two eyes of two patients, a diagnosis of Candida endophthalmitis was established by typical fundus appearance, positive vaginal culture, and, in one case, positive vitreous culture. After vitrectomy and intravitreal amphotericin B injection, one eye of one patient had a best-corrected visual acuity of 20/200, whereas one eye of one patient, who had systemic corticosteroid treatment before the correct diagnosis, developed recurrent retinal detachment and a best-corrected visual acuity of counting fingers. CONCLUSIONS: Induced abortion may cause endogenous Candida endophthalmitis in young healthy pregnant women. Systemic corticosteroid treatment may increase the risk of endophthalmitis.

Abortion, Induced↗
PubMed1998

A comparative study of the dose-response and time course of action of rocuronium and vecuronium in anesthetized adult patients.

STUDY OBJECTIVES: (1) To compare the dose-response relations of rocuronium and vecuronium in healthy adult patients anesthetized with nitrous oxide-oxygen-fentanyl-thiopental; and (2) to evaluate the time-course of action of two drugs following equipotent doses. DESIGN: Prospective, randomized, clinical comparison. SETTING: Operating room, Plastic Surgery Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College. PATIENTS: 60 ASA physical status I patients, aged 17-51 years, scheduled for elective plastic surgery. INTERVENTIONS: All patients were randomly assigned to either the rocuronium or vecuronium group. General anesthesia was induced with thiopental 4 to 6 mg/kg and fentanyl 2 to 4 micrograms/kg intravenously (i.v.), and maintained with 60% nitrous oxide (N2O) in oxygen. Further increments of thiopental or fentanyl were given as required. The dose-response relations of rocuronium and vecuronium were determined by the cumulative dose-response technique. MEASUREMENTS AND MAIN RESULTS: Neuromuscular function was assessed mechanomyographically with train-of-four (TOF) stimulation at the wrist every 12 seconds. The percentage depression of first twitch (T1) was used as the study parameter. The cumulative dose-response curve of vecuronium was shifted to the left in a parallel fashion compared with that of rocuronium. As assessed by linear regression, the potency ratio of vecuronium: rocuronium was 1:7.2. There were significant differences in the ED50, ED90, and ED95 between the two drugs. After i.v. administration of equipotent doses of both drugs (2 x ED90), the duration of peak effect, clinical duration, recovery index, and total duration were not significantly different between the two drugs. CONCLUSIONS: Compared with vecuronium, rocuronium is a low-potency, nondepolarizing relaxant, and its neuromuscular blocking potency is approximately 15% that of vecuronium in adult patients anesthetized with N2O and fentanyl. Following equipotent doses, the time-course of recovery for rocuronium is similar to that of vecuronium.

Adolescent↗
PubMed1998

Structural basis of CD8 coreceptor function revealed by crystallographic analysis of a murine CD8alphaalpha ectodomain fragment in complex with H-2Kb.

The crystal structure of the two immunoglobulin variable-like domains of the murine CD8alphaalpha homodimer complexed to the class I MHC H-2Kb molecule at 2.8 A resolution shows that CD8alphaalpha binds to the protruding MHC alpha3 domain loop in an antibody-like manner. Comparison of mouse CD8alphaalpha/H-2Kb and human CD8alphaalpha/HLA-A2 complexes reveals shared as well as species-specific recognition features. In both species, coreceptor function apparently involves the participation of CD8 dimer in a bidentate attachment to an MHC class I molecule in conjunction with a T cell receptor without discernable conformational alteration of the peptide or MHC antigen-presenting platform.

Amino Acid Sequence↗
PubMed1998

Successful pregnancy following very high-dose total body irradiation (1575 cGy) and bone marrow transplantation in a woman with acute myeloid leukemia.

A 22-year-old woman had a normal full-term delivery 6 years after a successful allogeneic bone marrow transplantation (BMT) for acute myeloid leukemia (AML). Conditioning therapy consisted of cyclophosphamide (120 mg/kg) and total body irradiation (TBI) to a total of 1575 cGy in seven fractions (225 cGy x 7, at a dose rate of 3.5 cGy/min). Graft-versus-host disease prophylaxis was with methotrexate and cyclosporin A. Grade I acute GVHD developed after BMT but there was no chronic GVHD. She became amenorrhoeic after BMT and serial gonadal testing indicated hypergonadotrophic hypogonadism. She became pregnant and delivered a full-term, healthy baby 6 years after BMT. Successful pregnancy after TBI of more than 1200 cGy is extremely rare. This case, to the best of our knowledge, is the second patient who received a higher dose of TBI (1575 cGy) to have a successful pregnancy. This and previous reports indicate that normal pregnancy is possible after BMT with TBI in excess of 1200 cGy.

Adult↗
PubMed1998

Inhibitory effects of Angelica pubescens f. biserrata on 5-lipoxygenase and cyclooxygenase.

Linoleic acid, osthol, osthenol and two polyacetylenes, falcarindiol and 11(S),16(R)-dihydroxyoctadeca-9Z,17-diene-12,14-diyn-1 -yl acetate were found to be the most active compounds responsible for the inhibitory activity of the dichloromethane extract of the roots of Angelica pubescens f. biserrata on 5-lipoxygenase (5-LO) and cyclooxygenase (COX-1) in vitro. They showed prominent inhibitory effect on 5-LO with IC50 values of 27.9 microM, 36.2 microM, 43.1 microM, 9.4 microM and 24.0 microM, respectively. Linoleic acid, osthenol, falcarindiol and 11(S), 16(R)-dihydroxyoctadeca-9Z,17-diene-12,14-diyn-1-yl acetate exhibited inhibitory activity on COX-1 with IC50 values of 13.3 microM, 64.3 microM, 66.0 microM and 73.3 microM.

Animals↗
PubMed1998

Influence of surgical technique on early postoperative hypoxaemia in children undergoing elective palatoplasty.

We have assessed the influence of different surgical procedures on the incidence, severity and duration of early postoperative hypoxaemia in 312 healthy infants and children undergoing elective palatoplasty. Group 1 patients underwent von Langenbeck palatoplasty (n = 149), group 2 patients underwent push-back palatoplasty (n = 124) and group 3 patients underwent combined push-back palatoplasty and superior pharyngeal flap surgery (n = 39). Arterial oxygen saturation (SpO2) was recorded while patients were breathing air shortly after arrival in the recovery room (0 min), and at 5, 10, 15, 20, 30, 40, 50, 60, 120 and 180 min thereafter. Patients who underwent more complex surgical techniques for palatoplasty had lower postoperative SpO2 values, slower recovery of SpO2 and a higher incidence of hypoxaemia during the early postoperative period. There were significant differences in postoperative SpO2, values and the incidence of hypoxaemia. The incidences of hypoxaemia and severe hypoxaemia were 27% and 1%, respectively, in group 1, 37% and 12% in group 2, and 36% and 33% in group 3. Hypoxaemia occurred most commonly in the first 15 min in children after von Langenbeck palatoplasty, in the first 40 min after push-back palatoplasty and in the 120 min after combined push-back palatoplasty and superior pharyngeal flap surgery. There were significant associations between low SpO2 values, incidence of hypoxaemia on admission to the recovery room and recovery scores.

Adolescent↗