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Biomedical subjects

Y Y Li

Publications and source records attributed to Y Y Li.

At least 55 records · Page 3Linked to original sources
PubMed1999

The prevalence of antibody to CagA in children is not a marker for specific disease.

BACKGROUND: In adults, a high prevalence of antibody to the cytotoxin-associated antigen (CagA) of Helicobacter pylori has been linked to the development of more serious gastroduodenal disease. Few investigators have examined this association in children. The purpose of this study was to investigate the seroprevalence of antibody to the CagA antigen as well as other specific H. pylori antigens in children. METHODS: By use of an immunoblot analysis kit, the immune response to specific H. pylori antigens in serum collected from 21 H. pylori-positive symptomatic Australian children, 5 with peptic ulcer disease and 16 with nonulcer dyspepsia, and 33 H. pylori-positive asymptomatic Chinese children. Sera from 20 H. pylori-negative symptomatic Australian children were used as control subjects. RESULTS: Antibody responses to the 26.5-kDa, 30-kDa, and 116-kDa (CagA) antigens were found to be the most prevalent, with 81.5%, 79.6%, and 76% of children, respectively, mounting a response. In contrast, antibody responses to the 19.5-kDa, 35-kDa, 45-kDa, 60-kDa, 89 kDa (VacA), and 180-kDa antigens occurred in 55.5%, 24%, 16.7%, 63%, 37%, and 7.4% of children, respectively. A higher prevalence of antibody response to CagA was found in the symptomatic Australian children with peptic ulcer disease (100%) compared with prevalence in those with nonulcer dyspepsia (56.3%), but the difference did not reach statistical significance. No significant difference was found between the prevalence of antibody to CagA in the Australian peptic ulcer disease group (100%) and that in the asymptomatic Chinese children (81.8%). CONCLUSION: These results suggest that in children CagA is not a marker of specific disease development.

Adolescent↗
PubMed1998

Differential expression of tissue inhibitors of metalloproteinases in the failing human heart.

BACKGROUND: Extracellular matrix turnover is regulated by matrix metalloproteinases (MMPs) and a family of tissue inhibitors of metalloproteinases (TIMPs). Together, these proteins may contribute to myocardial remodeling in congestive heart failure. We hypothesized that the expression of MMPs and TIMPs might be differentially regulated in the failing human heart. METHODS AND RESULTS: Northern blot analyses were performed with probes to TIMP-1 to -4 and GAPDH with poly A+ mRNA from ventricular tissues of patients with ischemic cardiomyopathy (ICM, n=16) or idiopathic dilated cardiomyopathy (DCM, n=15) and nonfailing control hearts (n=15). TIMP-1 to -4 and MMP-9 proteins were quantified by ELISA and/or Western blot, and the total gelatinolytic activity was studied by gelatin zymography. The results showed that cardiac expression of TIMP-1 and -3 transcripts and proteins was significantly reduced in ICM and DCM. No significant difference was observed in TIMP-2 and -4 transcripts. However, TIMP-4 protein was significantly reduced in ICM myocardium. MMP-9 protein content and total gelatinolytic activity were upregulated in the same samples. CONCLUSIONS: These studies demonstrated a selective downregulation of TIMPs along with upregulation of MMP-9 and gelatinolytic activity in the failing hearts, alterations that favor matrix degradation and turnover. These findings might be of pathophysiological significance and might suggest new therapeutic targets for limiting the ventricular remodeling and dilatation process characteristic of the failing human heart.

Adult↗
PubMed1998

IL-6 rescues enterocytes from hemorrhage induced apoptosis in vivo and in vitro by a bcl-2 mediated mechanism.

Following a hemorrhagic event, damage to the highly metabolic intestinal tissue induces loss of barrier function leading to bacterial escape and LPS contamination of the host. Orally administered IL-6 restores intestinal barrier function following hemorrhage in both rat and mouse models. IL-6 prevents apoptosis in a variety of lymphoid cells and lines, through the activation of the proto-oncogene bcl-2. This communication elucidates the role of the IL-6-bcl-2 interaction in intestinal apoptosis following hemorrhagic shock. Terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) and p53 immunohistochemical staining were used to examine intestines from mice hemorrhaged and fed saline or IL-6 and enterocytes (IEC-6) exposed to hypoxia and LPS alone or LPS and IL-6 in vitro. In situ hybridization for bcl-2 expression was performed on intestines or enterocytes. Intestinal sections from mice hemorrhaged and fed IL-6 showed reduction in apoptosis and increases in bcl-2 gene expression relative to sections taken from mice hemorrhaged and fed saline. IEC-6 cells exposed to hypoxia and LPS had high numbers of TUNEL staining cells. Subsequent exposure to IL-6 after hypoxia and LPS reduced apoptotic cell numbers and increased bcl-2 gene expression. The data show that exposure of intestinal epithelial cells to IL-6 either by oral administration in hemorrhaged mice or by coculture following hypoxia and LPS treatment results in increased bcl-2 gene expression and reduced damage from apoptosis.

Animals↗
PubMed1998

A low rate of reinfection following effective therapy against Helicobacter pylori in a developing nation (China).

BACKGROUND & AIMS: In developed countries, reinfection after successful eradication of Helicobacter pylori appears unusual. High prevalences of H. pylori in developing countries may result in high reinfection rates. The aim of this study was to determine the rate of reinfection and ulcer recurrence in Chinese patients cured of H. pylori and duodenal ulcer disease. METHODS: One hundred eighty-four patients with duodenal ulcer disease shown by endoscopic examination (1 month) and 14C-urea breath test (3 months) after termination of treatment to have cleared their H. pylori were investigated. Patients were followed up by endoscopy (12 and 24 months) and breath test (6, 9, 12, 18, and 24 months). H. pylori status at endoscopic examination was determined by rapid urease, histology, and culture. In reinfected patients, random amplification of polymorphic DNA fingerprinting was used to compare isolates before and after therapy. RESULTS: Four patients were reinfected with H. pylori over 24 months (3 within 6 months and 1 at 24 months; average annual recurrence rate, 1.08%). Fingerprinting of isolates from 3 patients showed 1 patient (6 months) to have identical strains and the remainder to have nonidentical strains before and after treatment. Ulcer relapse occurred in 6 patients (4 H. pylori positive). CONCLUSIONS: Reinfection with H. pylori is rare in developing countries where treatment is effective.

Adult↗
PubMed1998

IL-1 beta alters the expression of the receptor tyrosine kinase gene r-EphA3 in neonatal rat cardiomyocytes.

To identify proinflammatory cytokine responsive genes in the myocardium, we used differential display to study RNA isolated from neonatal rat cardiac myocytes treated with tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). Sequence analysis of differential display products confirmed by reverse Northern blots revealed one clone as the partial sequence of an Eph-related receptor tyrosine kinase (r-EphA3). In cardiac myocytes, 36-h exposure to TNF-alpha and IL-1 beta reduced r-EphA3 transcripts to 59.9% (P < 0.01) of control levels; this effect was largely dependent on IL-1 beta. Western blot analysis showed that changes in r-EphA3 protein levels reflect that seen for transcripts. Cardiac nonmyocytes expressed substantially lower levels of r-EphA3. Full-length r-EphA3 cDNA clone (3,077 base pair) yielded an amino acid sequence with 90-98% homology to the Eph receptor human EphA3, chick EphA3, and mouse EphA3. In the adult rat, r-EphA3 transcripts were most abundant in the heart, brain, and lung. These results suggest that IL-1 beta may exert its effect on cardiac myocytes at least in part by altering r-EphA3 expression.

Amino Acid Sequence↗
PubMed1998

3-Hydroxyphthaloyl beta-lactoglobulin. III. Antiviral activity against herpesviruses.

The spread of sexually transmitted diseases, including human immunodeficiency virus type 1 (HIV-1) and herpesvirus infections, has continued unabated despite educational efforts spearheaded as a response to the HIV-1 epidemic. This suggests the need for prophylactic measures, including the application of topical antiviral agents. Chemical modification of bovine beta-lactoglobulin (beta-LG), the major protein of whey, by hydroxyphthalic anhydride (3HP) led to the generation of a potent HIV-1 inhibitor (designated 3HP-beta-LG) shown to also have activity against herpes simplex virus types 1 and 2 (HSV-1, HSV-2). This report provides more detailed results concerning the anti-herpesvirus activity of 3HP-beta-LG, indicating that this compound: (i) inhibited infection by human cytomegalovirus (HCMV), which is known to be sexually transmitted; (ii) inactivated the infectivity of both HSV-1 and HSV-2; (iii) inhibited cell-to-cell transmission of HSV-1 and HSV-2; and (iv) bound to HSV-1, HSV-2 and HCMV virus particles and partially inhibited the binding of anti-glycoprotein E (gE) and anti-gC monoclonal antibodies to HSV-1 and HSV-2. The binding of 3HP-beta-LG to the herpesviruses under study was inhibited by aggregated human IgG, suggesting that the respective viral Fc receptor is one of the target sites for 3HP-beta-LG. In agreement with results on inhibition of HIV-1 infection, 3HP-beta-LG appears to be the acid anhydride-modified protein of choice as an antiviral agent against herpesviruses.

Animals↗
PubMed1997

T cell receptor-induced phosphorylation of Sos requires activity of CD45, Lck, and protein kinase C, but not ERK.

Stimulation of the T cell antigen receptor (TCR) activates signaling pathways involving protein kinases, phospholipase Cgamma1, and Ras. How these second messengers interact to initiate distal activation events is an area of intense scrutiny. In this report, we confirm that TCR ligation results in phosphorylation of Sos, a guanine nucleotide exchange factor for Ras. This requires expression of both the CD45 tyrosine phosphatase and the Lck protein tyrosine kinase and depends upon signaling via protein kinase C. In contrast to previous studies examining requirements for Sos phosphorylation following insulin and epidermal growth factor receptor engagement, we show that TCR-induced phosphorylation of Sos does not require activation of the mitogen-activated protein kinase/extracellular-signal regulated kinase (MEK/ERK) pathway. However, the basal phosphorylation of Sos in T cells is affected by either MEK or MEK-dependent kinases. Although Sos phosphorylation results in its dissociation from Grb2 following insulin stimulation in Chinese hamster ovary cells, TCR engagement on the Jurkat T cell line fails to elicit a similar effect. These data demonstrate that the kinases responsible for Sos phosphorylation differ following ligation of various cell surface receptors and that the consequences of Sos phosphorylation relies, at least in part, on sites of its phosphorylation.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Alloreactive cytotoxic T lymphocytes focus on specific major histocompatibility complex-bound peptides.

Alloreactive T cells are often specific for individual peptides that are bound to allogeneic major histocompatibility complex (MHC) molecules. Other alloreactive T cells are reported to be peptide-independent or to recognize MHC conformational changes that are induced by multiple peptides. We tested 12 anti-HLA-B7 alloreactive cytotoxic T lymphocyte (CTL) clones that bind a restricted region of HLA-B7, including three CTL clones that were generated in a protocol designed to stimulate peptide-independent T cells. All 12 CTLs recognized multiple point mutations in the HLA-B7 peptide-binding groove. Eleven of the 12 CTLs recognized specific peptides that eluted in one or two fractions on high-performance liquid chromatography (HPLC). None of the CTLs promiscuously recognized 16 HLA-B7-binding synthetic peptides, although one CTL recognized minor by-products in one synthetic peptide preparation. CTL clone KID-9 cross-reacted with allogeneic HLA-B7 and HLA-B27 molecules and recognized a distinct peptide bound to each MHC molecule. CTL clone KD-11 recognized peptides that eluted in two HPLC fractions and recognized HLA-B7-transfected peptide antigen processing defective T2 cells. These results indicate that CTL allorecognition is peptide-specific whether the allogeneic MHC molecules are expressed on normal cells or antigen processing-deficient cells.

Antigen Presentation↗
PubMed1997

Role of vagal fibers and bombesin/gastrin-releasing peptide-neurons in distention-induced gastrin release in rats.

In the rat the exact role of vagal fibers and the interaction between the extrinsic and intrinsic neural system in distention-induced gastrin release are still a matter of debate. Accordingly, the aim of the present study was to examine the contribution of afferent and efferent vagal fibers as well as intrinsic neurons on gastrin response to gastric distention. In anesthetized rats graded gastric distention by 5, 10 and 15 ml saline for 20 min caused a significant volume-dependent increase of plasma gastrin levels by 12+/-6 pg/ml (5 ml saline, n = 8, P =0.05), 26+/-7 pg/ml (10 ml saline, n = 10, P < 0.05) and 37+/-7 pg/ml (15 ml saline, n = 8, P < 0.01 ), respectively. To examine the role of the extrinsic vagal innervation, gastrin response to distention was studied in anesthetized rats after bilateral truncal vagotomy (n = 9) or selective afferent vagotomy following pretreatment with capsaicin (n = 6). Stimulation of gastrin release by 10 ml distention in sham-operated control rats was reversed to an inhibition after truncal vagotomy (26+/-7 vs. -11+/-4 pg/ml; P<0.05) and capsaicin-treatment (37+/-18 vs. -34+/-11 pg/ml; P<0.05). A contribution of cholinergic mechanisms to this vagovagal-mediated stimulation of distention-induced gastrin release was excluded, since atropine (100 microg/kg/h; n = 8) further augmented distention-stimulated gastrin release. Since bombesin/gastrin-releasing peptide (GRP)-neurons contribute to vagally stimulated gastrin secretion, we have examined gastrin response to distention in the presence of the specific bombesin-receptor antagonist D-Phe6-BN(6-13)OMe (400 microg/kg/h: n = 10). This bombesin-antagonist completely reduced distention-stimulated gastrin release in vivo. In contrast, distention of the isolated, extrinsically denervated stomach significantly decreased gastrin release by 13+/-5 pg/min (5 ml saline, n = 8, P < 0.05), 28+/-8 pg/min (10 ml saline, n = 11, P < 0.05) and 35+/-10 pg/min (15 ml saline, n = 8, P < 0.01), respectively, without changing the activity of bombesin/GRP-neurons. Distention-induced decrease of gastrin release was attenuated to 50 percent by atropine (10(-7) M: n = 10) or tetrodotoxin (TTX) (10(-6) M; n = 10), respectively. These data demonstrate, that in anesthetized rats distention-stimulated gastrin secretion depends on the activation of a vagovagal reflex and intrinsic bombesin/GRP-neurons. In contrast distention of the isolated rat stomach inhibits gastrin release in part via intrinsic cholinergic pathways and other as yet unknown mechanisms.

Animals↗
PubMed1997

Point mutations in mitochondrial DNA of patients with dilated cardiomyopathy.

Mitochondrial (mt) DNA mutations are hypothesized to be involved in the pathogenesis of dilated cardiomyopathy, because the mtDNA encodes 13 polypeptides that are essential for oxidative phosphorylation, upon which the heart relies for energy. To test this hypothesis, we amplified the mitochondrial genome by long PCR and then used restriction analysis and direct sequencing to examine 58 unrelated patients with dilated cardiomyopathy and 49 controls for the detection of point mutations. The results demonstrated that point mutations were significantly more frequent in the mtDNA of patients than in that of controls (173 in 58 patients v 54 in 49 controls, 2=16.51, P<0.001). In addition to normal variants and mutations common to both patients and controls, 43 mutations were identified only in patients. All but four of these mutations were homoplasmic. Mutations involving the evolutionarily conserved residues of cytochrome c oxidase subunit I, NADH dehydrogenase 5, tRNAAla and tRNAArg were identified. As many as 13 point mutations were found in an 8-month-old patient. In conclusion, there exist significantly more point mutations in mtDNA of patients than in controls, suggesting that multiple mutations may exert a cumulative effect on heart function. Thus, by altering the function of respiratory enzyme subunits or tRNAs, mtDNA point mutations could be relevant for the pathogenesis of dilated cardiomyopathy.

Adult↗
PubMed1997

The entire SU subunit is required for the incorporation of the HIV-1 envelope glycoprotein complex into virions.

A modified envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1) containing an intact TM subunit, but lacking most of the gp120/SU subunit was transported and expressed on the membrane of COS-1 cells. However, this deleted glycoprotein, failed to be incorporated into the budding viral particles. This suggested that a particular domain(s) of the gp120/SU glycoprotein subunit could be required for envelope incorporation. To explore this possibilty, we constructed envelope genes containing specific domains of the SU protein in-frame with the TM subunit. Transient expression studies indicated that any envelope primary translation product containing one or more of the gp 20/SU variable domains and the entire gp41/TM protein was transported and stably expressed on the cell surface. However, efficient proteolytic processing of these Env precursors into gp41, was not observed. The addition of more than 90% of the SU sequences into the deleted Env product, including the five variable domains, were insufficient to promote incorporation of this glycoprotein precursor into virions. These results suggest that the native conformation of the SU subunit is an essential requirement for the efficient incorporation of the Env complex into virons. The C1 domain of the SU glycoprotein subunit constitutes an important determinant that makes the envelope complex assembly-competent, but, by itself, it is not sufficient to drive this process.

Animals↗
PubMed1997

Systemic sepsis following hemorrhagic shock: alleviation with oral interleukin-6.

Gut-origin sepsis is a serious medical complication of military injuries following hemorrhage. Splanchnic ischemia induces intestinal necrosis leading to systemic bacteremia. Rat and mouse models of hemorrhagic shock were used to investigate bacterial translocation from the gut. Orally administered ameliorative treatments using the cytokine interleukin-6 (IL-6) were able to reduce or eliminate sepsis following hemorrhage. To mimic battlefield wounds and hemorrhage, anesthetized mice were bled from the femoral artery, held at a mean arterial blood pressure of 35 mm Hg for 1 hour, and then resuscitated with shed blood and 2-fold volume lactated Ringer's solution. Anesthetized rats were bled from the carotid artery at a rate of 15 ml/kg at 1 ml/minute. Bacteriological cultures of livers and mesenteric lymph nodes from hemorrhaged animals given recombinant IL-6 had significantly fewer colonies per gram of tissue than saline-fed controls. 125I-labeled IL-6 remained in the gut for up to 6 hours giving regional protection, whereas labeled interleukin-2 was disseminated throughout the body in the same time. In vivo and vitro studies of IL-6 showed that long incubations with high doses of trypsin, chymotrypsin, or intestinal contents were necessary to inactivate the bioactivity of this cytokine. Electron microscopy showed that epithelial cells from hemorrhaged mice fed saline had sparse or missing villi and vacuolated cytoplasm. Epithelial cells from control mice or mice hemorrhaged and fed cytokine appeared completely normal. Oral administration of IL-6 on the battlefield may be an important treatment for the prevention of sepsis following hemorrhage.

Administration, Oral↗
PubMed1997

Glycodelins GdA and GdS modified by 3-hydroxyphthalic anhydride inhibit gp120-CD4 binding and HIV-1 infection in vitro.

Bovine beta-lactoglobulin chemically modified with 3-hydroxyphthalic anhydride (3HP) was recently shown, at nanomolar concentrations, to block the binding site on CD4 for the HIV surface glycoprotein (gp120), potentially inhibiting HIV transmission. Human glycodelin has sequence homology with bovine beta-lactoglobulin and appears as different glycoforms in endometrium (GdA) and seminal plasma (GdS). We studied the anti-HIV effects of chemically modified GdA and GdS on both the infection of MT-2 cells by HIV-1IIIB, and the infection of peripheral blood mononuclear cells by the primary HIV isolate THA/93/051 belonging to subtype E. Whereas the native proteins were inactive when tested at physiologic concentrations, nanomolar concentrations of either 3HP-GdA or 3HP-GdS inhibited the production of HIV nucleocapsid p24, cytopathic effects of HIV-1IIIB, and infection of peripheral blood mononuclear cells by the primary HIV isolate THA/93/051. Moreover, both modified proteins inhibited gp120-CD4 binding, 3HP-GdS being more potent than 3HP-GdA (p = 0.0042). Because GdA and GdS have the same major protein core, the observed difference in gp120-CD4 binding must depend on the specific glycoform. In view of the previously reported contraceptive activity of GdA, the observed anti-HIV activity induced by its chemical modification should be of special interest in the development of antiviral strategies that may also have contraceptive effects.

Anti-HIV Agents↗
PubMed1996

Alloreactive anti-HLA-B7 cytolytic T cell clones use restricted T cell receptor genes.

Most alloreactive T cells specifically recognize peptides bound to donor MHC molecules. In addition to peptides, solvent accessible MHC residues also may stimulate alloreactive T cells. We studied T cell receptor (TCR) usage by 16 independent anti-HLA-B7 alloreactive cytolytic T lymphocyte (CTL) clones. Most or all of these CTL clones recognized unique peptides bound to HLA-B7. Despite the diversity of peptides recognized, 11 out of 15 CTL clones analyzed expressed TCR V(alpha) gene segment (AV) subgroups 1 and 3. Within AV subgroup 1, four of six clones expressed AV2; within AV subgroup 3, three clones used AV6. Ten of 14 CTL clones analyzed expressed V(beta) gene segment (BV) subgroups 4 and 1. In subgroup 4, BV14 was expressed by four of five alloreactive CTL clones. Similar AV and BV usage restriction was not found in mitogen-stimulated peripheral blood T cells from the major donor of the CTL clones. TCR A and TCR B junctional region sequences were quite diverse in length and sequence, although two CTL clones expressed nearly identical TCR B chains. We found no correlation between TCR AV or TCR BV usage and CTL recognition of 81 HLA-B7 variants. These results are consistent with models of TCR structure, in which very diverse TCR CDR3 regions contact very diverse peptides, and moderately diverse TCR CDR1 and CDR2 regions contact moderately diverse MHC alpha-helices.

Amino Acid Sequence↗
PubMed1996

CD40 ligation results in protein kinase C-independent activation of ERK and JNK in resting murine splenic B cells.

CD40 is a 45- to 50-kDa transmembrane glycoprotein that plays an important role in B cell proliferation, survival, memory, and Ig isotype switching. How CD40 engagement couples to these distal events in B cell activation remains poorly understood. In this study, we have examined signal transduction events mediated by CD40 cross-linking in resting murine splenic B cells. In comparison to signaling via the B cell Ag receptor (BCR), CD40 cross-linking was less effective at activating protein tyrosine kinases. Interestingly, however, CD40 engagement resulted in the phosphorylation of both extracellular signal-regulated protein kinase (ERK) and the Ras guanine nucleotide exchange factor, Son of sevenless. In addition, both ERK and c-Jun NH2-terminal kinase activities were increased after both CD40 and BCR ligation. Overnight treatment of cells with phorbol ester as well as pharmacologic inhibitors of protein kinase C abrogated these signaling events after BCR treatment; however, no effect was seen on CD40-mediated activation of ERK or c-Jun NH2-terminal kinase, suggesting that the BCR and CD40 differentially utilize protein kinase C to couple with these signaling pathways.

Animals↗