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S Wei

Publications and source records attributed to S Wei.

At least 181 records · Page 10Linked to original sources
PubMed1994

Identification of a novel human T-cell receptor V beta subfamily by genomic cloning.

Although a large number of human TCRBV gene segment sequences have been reported, the extent of the germline repertoire is still not precisely known. Most TCRBV gene segments have been identified in cDNA clones. However, genes expressed on only a small number of peripheral T cells may be more easily detectable by analysis of genomic DNA. In the present study, screening of cosmid clones containing the BV24S1 gene segment revealed the presence of a novel TCRBV gene segment defining a new subfamily, BV25S1. The nucleotide sequence of the gene contained a single open reading frame and encoded structurally important amino acids at correct positions. Southern blot analysis indicated that the BV25 subfamily contained only this single member. A single nucleotide polymorphism was identified by nucleotide sequencing of the gene from multiple individuals. Amplification of rearranged BV25S1 genes from cDNA derived from PBLs confirmed that the BV25S1 gene segment was capable of normal rearrangement and transcription.

Amino Acid Sequence↗
PubMed1994

Genetic and physical interactions between Srp1p and nuclear pore complex proteins Nup1p and Nup2p.

Nup1p is a yeast nuclear pore complex protein (nucleoporin) required for nuclear protein import, mRNA export and maintenance of normal nuclear architecture. We have used a genetic approach to identify other proteins that interact functionally with Nup1p. Here we describe the isolation of seventeen mutants that confer a requirement for Nup1p in a background in which this protein is normally not essential. Some of the mutants require wild-type Nup1p, while others are viable in combination with specific nup1 alleles. Several of the mutants show nonallelic noncomplementation, suggesting that the products may be part of a hetero-oligomeric complex. One is allelic to srp1 which, although it was identified in an unrelated screen, was shown to encode a protein that is localized to the nuclear envelope (Yano, R., M. Oakes, M. Yamaghishi, J. A. Dodd, and M. Nomura. 1992. Mol. Cell. Biol. 12:5640-5651). We have used immunoprecipitation and fusion protein precipitation to show that Srp1p forms distinct complexes with both Nup1p and the related nucleoporin Nup2p, indicating that Srp1p is a component of the nuclear pore complex. The distant sequence similarity between Srp1p and the beta-catenin/desmoplakin family, coupled with the altered structure of the nuclear envelope in nup1 mutants, suggests that Srp1p may function in attachment of the nuclear pore complex to an underlying nuclear skeleton.

Alleles↗
PubMed1994

Synergistic effects of fish oil diet and dimethylthiourea in acute adriamycin nephrosis.

The synergistic effects of combining fish oil (FO) diet, which reduces thromboxane A production, with the free radical scavenger, dimethylthiourea (DMTU), were evaluated in acute adriamycin nephrosis, because proteinuria in adriamycin nephrosis is mediated by increased renal thromboxane A and free radical production. The effects of combined evening primrose oil (EPO) and DMTU were compared with the DMTU + FO combination because EPO increases prostaglandin E but not thromboxane A. After 7, 14, and 21 days, proteinuria was significantly (p < 0.05) reduced in rats receiving either DMTU + corn oil (CO) or DMTU + FO compared with untreated control rats. However, after 21 days, rats receiving DMTU + FO had significantly reduced urine protein excretion compared with those receiving DMTU + CO (103.9 +/- 20 mg daily vs 351.8 +/- 29.8 mg daily; P < 0.05). In contrast to FO, rats receiving EPO + DMTU had similar urine protein excretion to rats receiving DMTU + CO after 21 days (170.2 +/- 20.34 mg daily vs 179.45 +/- 26.38 mg daily). The mean serum cholesterol concentration was significantly (P < 0.01) reduced in rats receiving DMTU + FO (195.2 +/- 23.8 mg/dL) compared with DMTU + CO (377.9 +/- 28.5 mg/dL). Serum triglyceride levels also were significantly (P < 0.01) reduced in rats receiving DMTU + FO (52.5 +/- 26.4 mg/dL) compared with DMTU + CO (100.5 +/- 36.9 mg/dL). No significant differences in serum cholesterol concentrations or triglycerides occurred between rats receiving DMTU + CO and DMTU + EPO. Renal glutathione content was significantly (P < 0.05) increased by 23% in normal rats receiving FO diet and by 34% in rats receiving combined DMTU + FO compared with CO alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Candida antigen titer is a marker of neutrophil dysfunction after severe injury.

UNLABELLED: Trauma patients with positive Candida antigen titers have high mortality rates. Death is the result of sepsis and multi-organ system failure. Considerations of host immunity to Candida led us to concurrently study the function of neutrophils (PMNs) from severely injured adults with positive titers (n = 20), patients with negative titers matched for age, sex, and injury (n = 20), and volunteers (n = 20). Anticandidal PMN function was determined using a 3H-glucose incorporation assay. RESULTS are expressed as mean percentage of growth inhibition +/- SEM. RESULTS: PMN, from all groups inhibited Candida growth, although PMNs from titer-positive patients demonstrated less growth inhibition. In vitro cytokines granulocyte macrophage-colony stimulating factor [(GM-CSF), interferon-gamma (IFN-gamma), and interleukin 8 (IL-8)] improved function of PMNs from each group and corrected the impaired anticandidal function of PMNs from titer-positive patients, with GM-CSF being most effective. CONCLUSIONS: Seriously injured patients with positive Candida antigen titers have PMNs with impaired anticandidal function, which can be restored by cytokines. These findings begin to explain why seriously injured patients with positive Candida antigen titers have increased mortality and to offer hope of therapeutic intervention.

Adult↗
PubMed1994

Monocytes overcome lymphocyte dysfunction in injured adults with elevated Candida antigen titers.

OBJECTIVE: Severely injured adults with elevated Candida antigen titers have increased mortality from sepsis, in part because of known neutrophil (PMN) dysfunction. Since PMN function is modulated by monocytes and lymphocytes, this study was undertaken to determine the ability of monocytes and lymphocytes isolated from injured adults with elevated Candida antigen titers to activate the anticandidal function of normal PMNs. METHODS: Lymphocytes with or without monocytes, isolated from 18 injured adults with elevated titers, were cultured in the presence or absence of heat-killed Candida albicans for 48 hours. Culture supernatants were harvested, diluted 1:40, 1:160, and 1:640, and tested for the ability to stimulate the anticandidal function of normal PMNs using an 3H-glucose incorporation assay. Monocytes and lymphocytes isolated from nine volunteers were studied for comparison. RESULTS: Supernatants of lymphocytes from healthy volunteers that were cultured with heat-killed C. albicans significantly augmented normal PMN anticandidal function. Supernatants of lymphocytes from injured adults with elevated titers that were cultured with heat-killed C. albicans did not significantly augment normal PMN anticandidal function. Supernatants of monocytes or lymphocytes from both groups of patients were able to upregulate PMN anticandidal function. CONCLUSIONS: Lymphocytes from injured adults with elevated Candida antigen titers are defective in their ability to stimulate PMN anticandidal function. Monocytes from these patients can respond to Candida exposure and overcome the lymphocyte functional defect seen in injured patients with elevated titers.

Adult↗
PubMed1994

Elevated Candida antigen titers are associated with neutrophil dysfunction after injury.

This study was undertaken to determine if impaired neutrophil (polymorphonuclear leukocytes [PMNL]) function is associated with an elevated Candida antigen titer after injury. PMNL from eight severely injured adults with Candida antigen titers of > or = 1:4 (titer positive) were evaluated for the ability to inhibit growth of Candida albicans in vitro by using a [3H]glucose incorporation assay. PMNL from eight severely injured adults with titers of < 1:4 (titer negative) and from eight healthy volunteers were studied for comparison. PMNL from the titer-positive patients had suppressed ability to inhibit C. albicans growth compared with PMNL from titer-negative patients and healthy volunteers. In vitro, PMNL function against C. albicans could be augmented significantly by cytokines. Granulocyte macrophage-colony-stimulating factor was most potent at augmenting function, followed by interleukin-8 and gamma interferon. Injured patients with elevated candida antigen titers have impaired PMNL function against C. albicans, and this function can be restored by cytokines.

Adult↗
PubMed1994

The Mycoplasma arthritidis superantigen MAM: purification and identification of an active peptide.

The prototypical superantigen MAM is an extracellular T-cell mitogen produced by Mycoplasma arthritidis, an organism which causes chronic proliferative arthritis of rodents. We here describe purification of MAM to homogeneity. Pure MAM exhibits all of the major properties previously described for partially purified MAM, including preference for H-2E molecules in presention to T cells, V beta T-cell receptor specificity for T-cell activation, and in vivo inhibition of T-cell functions but enhancement of B-cell activity as mediated by the superantigen bridge. Edman degradation of pure MAM gave a 54-residue partial amino-terminal sequence. The oligopeptide MAM15-31-C, synthesized according to the Edman sequence, blocked mitogenicity of MAM and supported assignment of the amino acid sequence.

Amino Acid Sequence↗
PubMed1994

[Effect of excessive fluoride intake on mental work capacity of children and a preliminary study of its mechanism].

We made an investigation in 157 children, aged 12-13, born and grew up in a coal burning pattern endemic fluorosis area and an experiment on excessive fluoride intake in rat. The results showed: (1) Excessive fluoride intake since early childhood would reduce mental work capacity (MWC) and hair zinc content: (2) The effect on zinc metabolism was a mechanism of influence on MWC by excessive fluoride intake; (3) Excessive fluoride intake decreased 5-hydroxy indole acetic acid and increased norepinephrine in rat brain; whether this is also a mechanism of the influence on MWC awaits confirmation.

Adolescent↗
PubMed1993

Coinduction of granulocyte-macrophage colony-stimulating factor release and lymphokine-activated killer cell susceptibility in monocytes by interleukin-2 via interleukin-2 receptor beta.

Human monocytes express interleukin-2 receptor beta (IL-2R beta) constitutively; however, the function of these receptors has not been fully delineated. We discovered that IL-2R beta directs two biologic activities in human monocytes, the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and increased susceptibility to lysis by lymphokine-activated killer cells (LAK) cells. Human monocytes were purified from peripheral blood mononuclear cells by plastic adherence and anti-CD2 plus complement lysis. By a 5-hour 51Cr-release assay, monocytes cultured in IL-2 were found to gain increasing susceptibility to LAK cells with time and this effect was dose dependent. Maximal susceptibility was obtained with a 4-day culture in 1,000 U/mL of IL-2. Monocytes were also found to release GM-CSF in response to IL-2 using a CSF-dependent cell line, Mo7e. Because IL-2-induced GM-CSF release coincides with LAK lysis of IL-2-cultured monocytes, we treated monocytes with anti-GM-CSF and anti-IL-2R beta to determine whether GM-CSF release and LAK susceptibility were dependent or independent events. We found that both phenomena were inhibited by either antibody. Therefore, we conclude that IL-2-induced release of GM-CSF is mediated by IL-2R beta, which then acts to modulate the susceptibility of monocytes to lysis by LAK cells.

Cytotoxicity, Immunologic↗
PubMed1993

Organization of human T-cell receptor beta-chain genes: clusters of V beta genes are present on chromosomes 7 and 9.

To ascertain the extent and organization of the germ-line human T-cell receptor (TCR) beta-chain gene repertoire, beta-chain variable region (V beta) genes were mapped by pulsed-field gel electrophoresis, cosmid cloning, and in situ hybridization. Probes derived from the 24 known V beta families were mapped to a total of six Sfi I fragments in DNA samples from multiple individuals representing all possible haplotypes of TCR V- and C (constant)-region insertion/deletion-related polymorphisms. Four of the Sfi I fragments were linked to one another to develop an extended map of the TCR beta-chain gene complex previously localized to chromosome 7q35. The remaining two Sfi I fragments, containing 6 V beta genes, could not be linked to the TCR beta-chain gene complex. Using human-hamster somatic cell hybrids and in situ hybridization, these orphon genes were localized to chromosome 9p. Nucleotide sequences of the orphon V beta genes, derived from cosmid clones, were 93-97% identical to V beta genes in the TCR beta-chain gene complex. Open reading frames in three of the orphon V beta genes were intact as were the recombination signal sequences. As expected, based on their orphon status, none of the V beta genes of chromosome 9 was detected in transcripts containing C beta. These results indicate that the functional germ-line V beta repertoire in humans is substantially (10%) smaller than previously estimated.

Animals↗
PubMed1993

Activation of tumor necrosis factor-alpha production from human neutrophils by IL-2 via IL-2-R beta.

In addition to T cells, NK cells, B cells, and monocytes, we provide new evidence that human polymorphonuclear neutrophils (PMN) can be functionally activated by IL-2 via binding to IL-2R beta expressed on the cell surface. Brief exposure of normal PMN to human rIL-2 enhanced both transcriptional and translational expression of TNF-alpha. The release of TNF-alpha protein by IL-2-treated PMN was inhibitable by a specific mAb against human IL-2-R beta. The response to IL-2 was dose and time dependent with the increase in TNF-alpha mRNA detected maximally 3 h after IL-2 exposure, followed by a continuous maintenance of high mRNA levels up to 18 h. The TNF-alpha mRNA was significantly increased above the medium control level, with as little as 10 U/ml of IL-2. Maximal transcription was obtained with 1000 U/ml of IL-2, which achieved the level observed with known neutrophil activating factors such as granulocyte-macrophage-CSF, IL-8, and Candida albicans. Using actinomycin D, it was found that new and continuous synthesis of a labile TNF-alpha mRNA was responsible for the observed high levels of transcripts. Of significance was the observation that cycloheximide could selectively modulate TNF-alpha mRNA transcription in neutrophils, depending on the cytokine used. Cycloheximide did not affect or alter TNF-alpha mRNA induction in IL-2-treated neutrophils but abrogated it in granulocyte-macrophage-CSF-treated neutrophils and superinduced transcription in C. albicans-treated neutrophils. Thus various control elements must be involved in the transcription of the TNF-alpha genes that are responsive to different cytokines and activating factors. The induction of TNF-alpha and functional activation of neutrophils by IL-2 is therefore an important immunomodulatory property of IL-2 that has not heretofore been recognized.

Antibodies, Monoclonal↗
PubMed1993

Effects of L-type calcium channel antagonists on the serotonin-depleting actions of MDMA in rats.

The calcium channel antagonists verapamil nifedipine and flunarizine all increased the threshold for convulsions induced by N-methyl-D-aspartate in rats. By contrast, only flunarizine blocked the long-term serotonin-depleting effects of 3,4-methylenedioxymethamphetamine. Flunarizine was also the only drug that antagonized methamphetamine-induced stereotypy. These findings suggest that calcium influx through L-type channels does not participate in the neurotoxic mechanism of MDMA, and that the neuroprotective actions of flunarizine are probably related to its anti-dopaminergic activity.

3,4-Methylenedioxyamphetamine↗
PubMed1993

Function associated with IL-2 receptor-beta on human neutrophils. Mechanism of activation of antifungal activity against Candida albicans by IL-2.

Polymorphonuclear neutrophils (PMN) are essential components of the host defense system against a wide variety of pathogens. We report here the novel finding that freshly isolated human PMN constitutively express detectable surface levels of IL-2R beta, but not IL-2R alpha, as analyzed by flow cytometry. Northern blot analysis confirmed the constitutive expression of mRNA for IL-2R beta in PMN. Scatchard analysis using 125I-labeled IL-2 demonstrated the presence of approximately 600 intermediate binding IL-2R per PMN, with a dissociation constant of 1.1 x 10(-9) M, similar to that of IL-2 binding to YT-1 tumor cells that specifically express IL-2R beta. More importantly, PMN were able to respond functionally to IL-2 by enhanced growth-inhibitory activity against an opportunistic fungal pathogen, Candida albicans. IL-2 activation of antifungal activity was dose-dependent, with some functional activation detected at 1 U/ml of rIL-2 and maximal activation at 1000 U/ml. The action of IL-2 was rapid, with maximal PMN activation after 30-min incubation with IL-2. The IL-2 enhancement of antifungal activity could be blocked by a specific antibody against IL-2R beta, but not by anti-IL-2R alpha. Analysis of the mechanism of IL-2 activation of PMN indicated that oxidative metabolism, as measured by superoxide anion production, was not involved. Instead, PMN release of lactoferrin appeared to be responsible for the heightened activity against C. albicans in IL-2-treated PMN. Not only was lactoferrin detected in the supernatants of IL-2-treated PMN, but also the antifungal activity of PMN activated by IL-2 could be blocked in the presence of antilactoferrin. These results, taken together, indicate that normal PMN are capable of functionally responding to IL-2 via expression of the IL-2R beta chain.

Animals↗
PubMed1993

Impaired polymorphonuclear leukocyte anticandidal function in injured adults with elevated Candida antigen titers.

Per protocol, adults with an Injury Severity Score of 18 or greater underwent Candida antigen titer measurements weekly. If titers were 1:4 or greater, neutrophil function against Candida albicans was determined with use of a tritiated glucose incorporation assay, and polymorphonuclear leukocytes obtained from healthy blood donors were studied concurrently for comparison. Polymorphonuclear leukocytes from healthy blood donors and injured patients with elevated titers were able to inhibit C albicans growth in a dose-dependent fashion. Polymorphonuclear leukocytes from injured patients with elevated titers had a significantly depressed ability to inhibit Calbicans growth compared with those from healthy blood donors at all effector cell-to-target cell ratios tested. Cytokine-treated polymorphonuclear leukocytes from healthy blood donors and injured patients with elevated Candida antigen titers demonstrated significantly improved anticandidal activity at all ratios of polymorphonuclear leukocytes-to-Candida. Granulocyte macrophage-colony stimulating factor was the most potent cytokine at reconstituting polymorphonuclear leukocyte function, followed by interferon gamma and interleukin 8. In conclusion, an elevated Candida antigen titer in injured adults is associated with impaired polymorphonuclear leukocyte antifungal activity. This depressed activity can be reconstituted by the addition of cytokine.

Adult↗