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Biomedical subjects

T Liu

Publications and source records attributed to T Liu.

At least 397 records · Page 22Linked to original sources
PubMed1994

The increased efficacy and decreased nephrotoxicity of a cyclosporine liposome.

A potential approach to avoid the complications of systemic immunosuppression is to deliver immunosuppressive agents locally to the site of the allograft. Liposomes are phospholipid particles that allow delivery of drugs preferentially to the reticuloendothelial system. Since the liver is a primary component of the RES, we hypothesized that liposome technology could be utilized to deliver immunosuppressive agents locally to a transplanted liver, thereby avoiding the complications of systemically delivered immunosuppression. We evaluated this hypothesis with a prototypic cyclosporine liposome in a rat model. Pharmacokinetic studies of this liposome indicated earlier clearance from the systemic circulation and increased hepatic uptake relative to the standard intravenous form of CsA. Decreased nephrotoxicity was also shown in an ischemic kidney model in the rat. The immunosuppressive efficacy of this liposome was also tested in a rat liver transplant model. There was a significant increase in survival compared with standard intravenous CsA when both drugs were administered at a dose of 1.75 mg/kg/day for seven days posttransplant (P < .05, CsA liposome-treated versus CsA/saline-treated). There were no demonstrable early toxic effects or late toxic effects observed with follow-up to 100 days. These data indicate that CsA liposomes have potential for use as an immunosuppressive agent with increased efficacy and decreased nephrotoxicity relative to the commercially available form of intravenous CsA. This improved therapeutic index of a locally targeted drug may lead to fewer complications attributed to systemic immunosuppression.

Animals↗
PubMed1994

Comparison of suicide rates among industrial groups.

Suicide rates among industrial groups were examined systematically using death certificate data from 1984 through 1989 in Alabama. Poisson log-linear modelling was used to estimate the rate ratios (RR) of industries compared to a referent and to adjust for confounding. Marked differences in suicide rates were found among industrial groups. The rates ranged from 5.31 to 62.36 per 100,000 population per year. People employed in public administration had the lowest rate. In comparison with public administration, the construction industry had the highest risk (adjusted RR = 11.8, 95% confidence interval (CI): 9.6-14.6). Employees of the mining industry experienced a similarly high risk (adjusted RR = 11.5, 95% CI: 8.2-16.3). Persons employed in farming, agriculture services, forestry, and fisheries, manufacturing, and transportation, communications, and other public utilities industries had intermediate risks. Smaller elevations of suicide rates compared to public administration were observed in the wholesale trade, retail trade, finance, insurance, and real estate, and services industries. The differences of suicide rates may be related to sociodemographic differences, self-selection for occupation, ease of access to lethal agents, or job stress.

Alabama↗
PubMed1994

Presentation of viral antigens restricted by H-2Kb, Db or Kd in proteasome subunit LMP2- and LMP7-deficient cells.

In the class II region of the major histocompatibility complex (MHC(, four genes implicated in MHC class I-mediated antigen processing have been described. Two genes (TAP1 and TAP2) code for multimembrane-spanning ATP-binding transporter proteins and two genes (LMP2 and LMP7) code for subunits of the proteasome. While TAP1 and TAP2 have been shown to transport antigenic peptides from the cytosol into the endoplasmic reticulum, where the peptides associate with MHC class I molecules, the role of LMP2/7 in antigen presentation is less clear. Using antigen processing mutant T2 cells that lack TAP1/2 and LMP2/7 genes, it was recently shown that expression of TAP1/2 alone was sufficient for processing and presentation of the influenza matrix protein M1 as well as the minor histocompatibility antigen HA-2 by HLA-A2. To understand if presentation of a broader range of viral antigens occurs in the absence of LMP2/7, we transfected T2 cells with TAP1, TAP2 and either of the H-2Kb, Db or Kd genes and tested their ability to present vesicular stomatitis vires and influenza virus antigens to virus-specific cytotoxic T lymphocytes. We found that T2 cells, expressing TAP1/2 gene products, presented all tested viral antigens restricted through either the H-2Kb, Db or Kd class I molecules. We conclude that the proteasome subunits LMP2/7 as well as other gene products in the MHC class II region, except from TAP1/2, are not generally necessary for presentation of a broader panel of viral antigens to cytotoxic T cells. However, the present results do not exclude that LMP2/7 in a more subtle way may, or in rare cases completely, affect processing of antigen for presentation by MHC class I molecules.

Animals↗
PubMed1994

Determination of the structure of the DNA binding domain of gamma delta resolvase in solution.

The DNA binding domain (DBD) of gamma delta resolvase (residues 141-183) is responsible for the interaction of this site-specific DNA recombinase with consensus site DNA within the gamma delta transposable element in Escherichia coli. Based on chemical-shift comparisons, the proteolytically isolated DBD displays side-chain interactions within a hydrophobic core that are highly similar to those of this domain when part of the intact enzyme (Liu T, Liu DJ, DeRose EF, Mullen GP, 1993, J Biol Chem 268:16309-16315). The structure of the DBD in solution has been determined using restraints obtained from 2-dimensional proton NMR data and is represented by 17 conformers. Experimental restraints included 458 distances based on analysis of nuclear Overhauser effect connectivities, 17 phi and chi 1 torsion angles based on analysis of couplings, and 17 backbone hydrogen bonds determined from NH exchange data. With respect to the computed average structure, these conformers display an RMS deviation of 0.67 A for the heavy backbone atoms and 1.49 A for all heavy atoms within residues 149-180. The DBD consists of 3 alpha-helices comprising residues D149-Q157, S162-T167, and R172-N183. Helix-2 and helix-3 form a backbone fold, which is similar to the canonical helix-turn-helix motif. The conformation of the NH2-terminal residues, G141-R148, appears flexible in solution. A hydrophobic core is formed by side chains donated by essentially all hydrophobic residues within the helices and turns. Helix-1 and helix-3 cross with a right-handed folding topology. The structure is consistent with a mechanism of DNA binding in which contacts are made by the hydrophilic face of helix-3 in the major groove and the amino-terminal arm in the minor groove. This structure represents an important step toward analysis of the mechanism of DNA interaction by gamma delta resolvase and provides initial structure-function comparisons among the divergent DBDs of related resolvases and invertases.

Amino Acid Sequence↗
PubMed1994

Suicide in Alabama, 1980 to 1989.

Trends of US suicide rates show great variations among demographic groups over time. Although more attention has been directed to the increasing suicide rate among adolescents, persons aged 65 years and older continue to commit suicide at a higher rate than for any other age group. To examine the recent trend of suicide rates and compare the suicide pattern with that at the national level, we conducted a study using suicide data in Alabama from 1980 to 1989. For all age groups in Alabama in the 1980s, male suicide rates exceeded female rates. Of the four major race-sex groups, nonwhite females are an especially low-risk group, experiencing a rate of about 1.5/100,000 at all ages. There have been remarkable increases in suicide rates in the 1980s for males, especially for nonwhite males in Alabama. The results suggest that high-risk groups to be targeted for interventions are men over age 45 (especially white men over age 65), and divorced and widowed men and women.

Adolescent↗
PubMed1994

Tumor necrosis factor-alpha expression in ischemic neurons.

BACKGROUND AND PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) is a cytokine with diverse proinflammatory actions, including endothelial leukocyte adhesion molecule expression. Since leukocytes infiltrate into ischemic brain lesions, the present study was conducted to examine whether TNF-alpha messenger RNA (mRNA) and peptide are expressed in the brain after experimental focal stroke and before leukocyte accumulation. METHODS: TNF-alpha mRNA and protein expression were monitored in the ischemic and nonischemic cerebral cortex of rats after focal ischemia produced by permanent middle cerebral artery occlusion. The effect of TNF-alpha administered by microinjection into the brain cortex on leukocyte adherence to brain capillaries was also studied. RESULTS: Induction of TNF-alpha mRNA, normalized to a standard reference rat macrophage TNF-alpha mRNA, was detected as early as 1 hour after middle cerebral artery occlusion. TNF-alpha mRNA was elevated by 3 hours (29 +/- 6% versus 2 +/- 1% in sham-operated rats) only in the ischemic cortex, with peak expression at 12 hours (104 +/- 8%; P < .01). Five days after middle cerebral artery occlusion, TNF-alpha mRNA levels in ischemic cortex were still significantly elevated (38 +/- 5%; P < .05). Also, TNF-alpha mRNA expression was greater in the ischemic cortex of spontaneously hypertensive rats than in normotensive rats (P < .05). Double-labeling, immunohistochemical studies revealed the presence of TNF-alpha protein localized within nerve fibers in the evolving infarct at 6 and 12 hours after ischemia and further expression in the tissues immediately adjacent to the infarct 24 hours after ischemia. After 5 days, the neuronally localized peptide had diminished greatly, but macrophages located within the infarcted tissues were immunoreactive. Cortical microinjections of TNF-alpha (10 ng in 1 microL) produced a significant neutrophil adherence/accumulation in capillaries and small blood vessels 24 hours later. CONCLUSIONS: These results represent the first demonstration that focal cerebral ischemia in rats results in elevated TNF-alpha mRNA and protein in ischemic neurons. The neuronal expression of peptide appears to facilitate the infiltration of inflammatory cells that can further exacerbate tissue damage in cerebral ischemia and might contribute to increased sensitivity and risk in focal stroke.

Animals↗
PubMed1994

Localization of a pernicious anaemia autoantibody epitope on the alpha-subunit of human H,K-adenosine triphosphatase.

Four cDNA fragments encoding different portions of the alpha-subunit of human H,K-adenosine triphosphatase (ATPase) were amplified by means of the polymerase chain reaction technique, ligated into the plasmid pGEX-2T, and expressed as glutathione S-transferase fusion proteins in Escherichia coli. The fragments A (residues 163-313), Ba (residues 360-797), Bb (residues 526-797), and C (residues 822-1031) together encompass 77% of the alpha-subunit and cover most of its cytosolic part. The reactivities of autoantibodies in the sera from patients with pernicious anaemia with the recombinant fusion proteins were analysed by immunoblotting. One autoantigenic epitope was found in the NH2-terminal part of the Ba fragment--that is, between residues 360 and 525. No epitope was detected in the other fragments. The Ba fragment was cleaved off from the glutathione S-transferase fusion protein by the action of thrombin and was then further purified. By means of enzyme-linked immunosorbent assay, 28 of 42 sera (67%) from patients with pernicious anaemia were positive against the purified Ba fragment. The present results provide a final proof that the human H,K-ATPase alpha-subunit is a major autoantigen in the parietal cell and that the major epitope is located between residues 360 to 525 on the cytosolic side of the secretory membrane.

Adult↗
PubMed1994

[The primary observation of effect on immune function of human body by YAG laser tonsillocoagulation].

Tonsillocoagulation was performed on 50 patients with chronic tonsillitis by virtue of YAG Laser. The patients' serum IgG, IgA, IgM, C3level and some acute phase reactant proteins (APRPs) including alpha 1-AGP, alpha 1-AT, Tf were measured pre- and postoperatively. In addition, tonsillar morphology was observed with light and electron microscope before and after tonsillocoagulation. Following up the patients for six to twelve months, we discovered that their immune function remained normal and that their symptoms of chronic tonsillitis had been controlled, it suggests that YAG Laser tonsillocoagulation can be a practical therapy for chronic tonsillitis.

Acute-Phase Proteins↗
PubMed1994

[The experimental study of immunosuppressive effect of tripchlorolide on the cardiac allograft rats].

In order to confirm the anti-rejection effect of Tripchlorolide (T4), we compared the mean survival time of cardiac allograft, scores of pathological damage of the heart, the generation of IL-2 from splenocytes stimulated by ConA, and the serum level of sIL-2R in the heart transplant model (Lou-->F344) that received either cyclosporine or T4. The present study has shown that T4 could prolong the MST of cardiac allograft and significantly decrease the degrees of pathological damage of the transplant heart. The results indicated that T4 might be used as new anti-rejection drug in organ transplantation.

Animals↗
PubMed1994

Down-regulation of c-myc oncogene during NGF-induced differentiation of neuroblastoma cell lines.

There may be a close relationship between myc oncogenes and carcinogenesis of human neuroblastoma. In previous studies, we were able to induce differentiation of certain neuroblastoma cell lines with NGF. In order to study gene regulation during differentiation, N-myc and c-myc cDNA probes were hybridized with RNA extracted from different cell lines before and after NGF treatment. It was found that cell lines which expressed N-myc did not express c-myc while those with c-myc did not express N-myc except for SHEP cell line which had neither c-myc nor N-myc expression. In NGF-induced differentiated neuroblastoma cells, c-myc oncogene was down-regulated in comparison with the control samples. The time course of c-myc down-regulation was concomitant with the appearance of morphological differentiation. In situ hybridization also showed remarkable reduction of c-myc oncogene expression in NGF-induced differentiated cells as compared with the untreated control cells. These results indicate that down-regulation of c-myc oncogene may be a key event during NGF-induced differentiation and over-expression of c-myc oncogene may, at least partially, be responsible for the genesis of neuroblastoma.

Cell Transformation, Neoplastic↗
PubMed1994

[Gene expression of EGFR, EGF and TGF alpha in human colonic carcinoma cell lines].

Gene expression of epidermal growth factor receptor (EGFR), epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) in human colonic carcinoma cell lines (HT10, LST174 and Lovo) was studied by using Northern blot technique. Total RNAs were isolated from these cell lines, separated by 1% agarose gel electrophoresis, transferred onto a membrane and hybridized with EGFR, EGF and TGF alpha probes. EGF and EGFR mRNAs were found in all three cell lines, and TGF alpha mRNA was seen in LST174 and HT10 cell lines but not in Lovo. The results indicate that autocrine stimulation by growth factor exists in human colonic carcinoma cell lines and it may be one of the important causes for the uncontrolled growth of carcinoma cell.

Blotting, Northern↗
PubMed1994

Cytokines, inflammation, and brain injury: role of tumor necrosis factor-alpha.

The cytokine tumor necrosis factor (TNF-alpha) is a pleotrophic polypeptide that plays a significant role in brain immune and inflammatory activities. TNF-alpha is produced in the brain in response to various pathological processes such as infectious agents [e.g., human immunodeficiency virus (HIV) and malaria], ischemia, and trauma. TNF-alpha mRNA is rapidly produced in response to brain ischemia within 1 h, reaches a peak at 6-12 h post ischemia, and subsides 1-2 days later. TNF-alpha mRNA expression corresponds in a temporal fashion to other cytokines such as interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (KC), and IL-1 and precedes the infiltration of inflammatory cells into the injured zone. TNF-alpha is present early in neuronal cells in and around the ischemic tissue (penumbra), yet at later time points, the peptide is found in macrophages in the infarcted tissue. TNF-alpha has been demonstrated to cause expression of proadhesive molecules on the endothelium, which results in leukocyte accumulation, adherence, and migration from capillaries into the brain. Furthermore, TNF-alpha activates glial cells, thereby regulating tissue remodeling, gliosis, and scar formation. Thus, evidence is emerging in support of a role for TNF-alpha in injury induced by infectious, immune, toxic, traumatic, and ischemic stimuli. TNF-alpha promotes inflammation by stimulation of capillary endothelial cell proinflammatory responses and thereby provides leukocyte adhesion and infiltration into the ischemic brain. The evidence generated so far suggests that agents that suppress TNF-alpha's production or actions will reduce leukocyte infiltration into ischemic brain regions and thereby diminish the extent of tissue loss.

Brain↗
PubMed1994

Treatment of metastatic prostate carcinoma with radiolabeled antibody CC49.

UNLABELLED: A Phase II trial of 75 mCi/m2 131I-anti-TAG-72 high-affinity antibody CC49 was studied in 15 patients with hormone-resistant metastatic prostate cancer. METHODS: Patients had adequate renal, liver and hematopoietic function. No previous cytotoxic chemotherapy was allowed and previous radiation was limited to 20% of the active bone marrow. RESULTS: No acute adverse reactions occurred, but all patients had evidence of an immune response to CC49 by 4 wk. Six of 10 symptomatic patients had bone pain relief, but no patients met the radiographic or PSA criteria for objective response. Positive imaging of bone and/or soft-tissue lesions was noted for 13 of the 15 patients. CONCLUSIONS: CC49 had a high frequency of tumor localization with evidence of anti-tumor effects (pain relief).

Adenocarcinoma↗