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Biomedical subjects

F Liu

Publications and source records attributed to F Liu.

At least 397 records · Page 22Linked to original sources

Gestational and smoking effects on peptidase activity in the placenta.

Angiotensin converting enzyme (ACE) and leucine aminopeptidase (LAP) regulate fetally and maternally generated peptides in the placenta. In this study, ACE-like activity was found to be decreased and LAP-like activity increased with increasing days of gestation in rat placental tissues forming the fetal:maternal interface. Membrane-associated ACE-like and LAP-like activities in the placenta of smokers were also found to be significantly higher than their respective activities in placenta of nonsmokers. Our collective findings suggest that gestational and environmentally-induced changes in placental peptidase activities may account for variable peptide hormone and/or therapeutic peptide metabolism in the placenta.

Animals↗

Inhibition of viral gene expression by human ribonuclease P.

External guide sequences (EGSs) are small RNA molecules which consist of a sequence complementary to a target mRNA and render the target RNA susceptible to degradation by ribonuclease P (RNase P). EGSs were designed to target the mRNA encoding thymidine kinase (TK) of herpes simplex virus 1 for degradation. These EGSs were shown to be able to direct human RNase P to cleave the TK mRNA sequence efficiently in vitro. A reduction of about 80% in the expression level of both TK mRNA and protein was observed in human cells that steadily expressed an EGS, but not in cells that either did not express the EGS or produced a "disabled" EGS which carried a single nucleotide mutation that precluded RNase P recognition. Thus, EGSs may represent novel gene-targeting agents for inhibition of gene expression and antiviral activity.

Animals↗

Enhanced gene expression in mouse lung by prolonging the retention time of intravenously injected plasmid DNA.

The effect of retention time of plasmid DNA in mouse lung on the level of transgene expression after intravenous administration was examined. Using CMV driven expression system with luciferase gene as a reporter and preinjection of free cationic liposomes into the animal as means of manipulating the retention time of plasmid DNA, we demonstrated that naked plasmid DNA is effective in transfecting cells in the lung by intravenous administration. An increase in DNA retention time in the lung results in a higher level of gene expression. Liposomes composed of cationic lipids with alkyl chains exhibited better activity than cholesterol-based cationic liposomes to retain the plasmid DNA in the lung. The level and patterns of gene expression obtained appeared similar to those seen in animals transfected by DNA-liposome complexes. These results suggest that prolonging the exposure time of DNA to the target cells in vivo may be an important strategy in achieving a high level of gene expression. Our data also introduce a possibility that the function of cationic liposomes in lipoplex-mediated transfection in vivo is to extend the interaction time of DNA with the cells.

Animals↗

Hypertonic saline resuscitation diminishes lung injury by suppressing neutrophil activation after hemorrhagic shock.

UNLABELLED: Hypertonic saline (HS) resuscitation after hemorrhage and sepsis has been shown to markedly reduce the development of lung injury in animals, compared with traditional resuscitation with lactated Ringer's (LR). These experiments examined the effect of HS on lung injury after hemorrhage without sepsis. The effects of HS and LR resuscitation on neutrophil trafficking, neutrophil adhesion, and neutrophil oxidative burst were studied. METHODS: BALB/c mice were hemorrhaged to a mean arterial pressure of 40 torr for 1 h. Animals were resuscitated with shed blood and either 4 mL/kg of 7.5% HS or LR in twice the volume of the shed blood. Lung histology was examined 24 h after hemorrhage. Lung myeloperoxidase content and bronchoalveolar lavage fluid neutrophil counts were obtained. Peripheral blood smears were obtained to determine the neutrophil percentage. Peripheral blood neutrophil CD11b expression and neutrophil H2O2 production were assayed by flow cytometry. RESULTS: HS animals had less lung injury than LR animals. The mean myeloperoxidase activity in HS versus LR animals was 1.79+/-1.33 U/100 mg versus 3.0+/-1.33 U/100 mg, respectively. The percentage of neutrophils in the bronchoalveolar lavage fluid of HS animals (3.8%+/-.8) was significantly less than that of LR animals (10.8%+/-2.1). This corresponded to a significantly higher peripheral blood neutrophil count in HS animals compared with LR animals, 41% vs. 20%, respectively. There was no difference in neutrophil expression of the CD11b integrin between the HS and LR groups. The neutrophils of LR animals had basal H2O2 production that was 107% greater than that of controls; HS suppressed this hemorrhage-induced activation by > 60%. HS resuscitation after hemorrhagic shock protects against the development of lung injury. This protection is due, in part, to suppression of the hemorrhage-induced neutrophil oxidative burst. HS resuscitation offers immunomodulatory potential after hemorrhagic shock.

Animals↗

Transformation suppression by protein tyrosine phosphatase 1B requires a functional SH3 ligand.

We have recently shown that protein tyrosine phosphatase 1B (PTP1B) associates with the docking protein p130Cas in 3Y1 rat fibroblasts. This interaction is mediated by a proline-rich sequence on PTP1B and the SH3 domain on p130Cas. Expression of wild-type PTP1B (WT-PTP1B), but not a catalytically competent, proline-to-alanine point mutant that cannot bind p130Cas (PA-PTP1B), causes substantial tyrosine dephosphorylation of p130Cas (F. Liu, D. E. Hill, and J. Chernoff, J. Biol. Chem. 271:31290-31295, 1996). Here we demonstrate that WT-, but not PA-PTP1B, inhibits transformation of rat 3Y1 fibroblasts by v-crk, -src, and -ras, but not by v-raf. These effects on transformation correlate with the phosphorylation status of p130Cas and two proteins that are associated with p130Cas, Paxillin and Fak. Expression of WT-PTP1B reduces formation of p130Cas-Crk complexes and inhibits mitogen-activated protein kinase activation by Src and Crk. These data show that transformation suppression by PTP1B requires a functional SH3 ligand and suggest that p130Cas may represent an important physiological target of PTP1B in cells.

Animals↗

Suppressive effect of oestradiol on chemical hepatocarcinogenesis in rats.

AIMS: To examine the effects of oestradiol and testosterone on the early carcinogenic changes expressed in rat liver from the diethylnitrosamine (DEN), 2-acetylaminofluorene (AAF), partial hepatectomy (PH) model of hepatocarcinogenesis. METHODS: Preneoplastic liver lesions were evaluated using immunohistochemical analysis of glutathione-S-transferase placental form (GST-P) expression; oestrogen and androgen receptor levels were measured by radioimmunoassay. RESULTS: Oestradiol administration to non-castrated DEN-AAF-PH treated males resulted in a decrease in the area of GST-P positive foci, while testosterone increased the serum oestradiol level and reduced the area. In males, castration alone and castration with oestradiol replacement significantly reduced the GST-P positive area, and increased the hepatic oestrogen receptor level. In DEN-AAF-PH treated females, castration with testosterone replacement was associated with a significant increase in the GST-P positive area and the hepatic androgen receptor level. CONCLUSION: These findings suggest that exogenous and endogenous oestradiol can suppress chemical hepatocarcinogenesis. It appears that oestrogen receptors may be involved in the inhibition of malignant transformation of preneoplastic liver cells, while androgens and androgen receptors are involved in hepatocarcinogenesis.

2-Acetylaminofluorene↗

Disturbances of growth hormone-insulin-like growth factor axis and response to growth hormone in acidosis.

Severe chronic metabolic acidosis (CMA) in rats is associated with poor food intake and downregulation of growth hormone (GH), insulin-like growth factors (IGFs), and liver receptors; the administration of recombinant GH (rGH) fails to improve the growth failure. In mice with carbonic anhydrase II deficiency (CAD), a model of moderate CMA with food intake close to normal, we studied serum levels of GH, IGFs, and IGF-binding proteins, and the growth response to rGH. CAD was associated with low serum levels of GH in males. Randomized administration of rGH from approximately 5 to approximately 12 wk to CAD mice improved food efficiency and increased serum IGF-I levels, final length, and weight compared with placebo without affecting blood pH. Although administration of rGH also increased linear growth in healthy animals, the effect was less than that in CAD mice and was only observed when started before 6 wk of life. Thus growth failure in CAD mice is associated with a decrease in GH secretion in males but not in females. Long-term administration of rGH increases linear growth in CAD mice despite persistent CMA.

Acidosis↗

Regulation of renal parathyroid hormone receptor expression by 1, 25-dihydroxyvitamin D3 and retinoic acid.

The renal distal convoluted tubule (DCT) is the major site of parathyroid hormone (PTH) and 1alpha,25-dihydroxyvitamin D3 [1, 25(OH)2D3]-regulated calcium absorption. 1,25(OH)2D3 augments PTH-stimulated calcium transport by DCT cells, while having no effect of its own. 1,25(OH)2D3 mediates its effects on gene expression by binding to a nuclear vitamin-D receptor (VDR), which then associates with the retinoid-X receptor (RXR) as a heterodimer. We studied the effects of 1,25(OH)2D3, 9-cis- and all-trans-retinoic acid on PTH/PTHrP receptor expression. mRNAs for the PTH/PTHrP, VDR, and RXR receptors were detected in immortalized DCT cells by reverse transcriptase-polymerase chain reaction. Changes in PTH/PTHrP receptor mRNA expression were quantified by slot blot hybridization. 1,25(OH)2D3 maximally increased PTH/PTHrP receptor mRNA levels by 70%. The stimulation was specific since 1,25(OH)2D3 treatment had no effect on the expression of adrenergic receptor or Na+/H+ exchanger mRNA levels. Likewise, the inactive form, 25(OH)2D3 had no effect on PTH/PTHrP receptor mRNA expression. In combination with the putative RXR ligand, 9-cis-retinoic acid, 1,25(OH)2D3 increased PTH/PTHrP receptor mRNA levels 4-fold. 9-cis-Retinoic acid had no effect of its own on steady-state PTH/PTHrP receptor mRNA expression. The putative ligand for the retinoic acid receptor, all-trans-retinoic acid, increased PTH/PTHrP receptor mRNA expression alone and in combination with 1,25(OH)2D3. 9-cis-Retinoic acid alone, and in combination with 1,25(OH)2D3, also increased specific PTH/PTHrP receptor binding to plasma membranes isolated from DCT cells. These results indicate that 1,25(OH)2D3 upregulated PTH/PTHrP receptor expression at both mRNA and protein levels in a manner consistent with VDR/RXR heterodimers transactivating the PTH/PTHrP receptor gene by binding a vitamin D response element in the PTH/PTHrP gene.

Alitretinoin↗

Activity-regulated phosphorylation of cAMP response element binding protein in the developing striatum: implications for patterning the neurochemical phenotypes of striatal compartments.

A distinct feature of the striatum is that much of the expression of neurochemicals in this forebrain structure follows a compartmental (striosome/matrix) ordering. How this pattern of neurochemical compartmentation is developed and regulated is still unknown. In the present paper we propose that a key feature of this early striatal plasticity is differential control of the activation kinetics of the cAMP response element binding protein (CREB), which in turn influences striatal expression of genes containing cAMP response elements in their promoter sequences. Specifically, we propose that activity-dependent regulation of the kinetics of CREB phosphorylation, brought about early expressed protein phosphatases and protein phosphatase inhibitors in the developing striatal compartments, helps to set up and to maintain patterning of the neurochemical prototypes characteristic of striatal compartments.

Aging↗

The insulin-like growth factor axis and growth in children with chronic renal failure: a report of the Southwest Pediatric Nephrology Study Group.

Children with chronic renal failure (CRF) are often growth recarded despite normal serum levels of GH and insulin-like growth factors (IGFs). Recent studies suggest that excess IGF-binding proteins (IGFBPs) in the 35-kDa fractions of CRF serum contribute to CRF growth failure. This report characterizes the relationship between IGFBP-3 and IGF peptides in the serum of growth-retarded CRF children. Size-exclusion chromatography at pH 7.4 found IGFBP-3 and IGFs almost exclusively in the 150-kDa fractions of normal serum, where their molar stoichiometry was approximately 1:1. However, similar chromatography of CRF serum found a molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions and large amounts of IGFs in the 35-kDa fractions. In the 150-kDa fractions of CRF serum, IGFBP-3 was present in normal amounts, but a greater than normal amount was in the form of a 29-kDa IGFBP-3 fragment. Treatment of these CRF children with recombinant human GH increased the molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions, the amount of IGFBP-3 and total IGFs in the 150-kDa fractions, and the amount of IGFs, but not IGFBPs, in the 35-kDa fractions. These data suggest that in untreated CRF children, proteolysis of IGFBP-3 in the 150-kDa fractions releases IGFs to the excess IGFBPs in the 35-kDa fractions, but insufficient IGF is released to overcome the growth-inhibiting effects of these excess IGFBPs. Treatment with recombinant human GH increases levels of IGFs and IGFBP-3 in the 150-kDa fractions, and subsequent IGFBP-3 proteolysis releases sufficient IGF to overcome the growth inhibitory effects of excess IGFBPs in the 35-kDa fractions of CRF serum.

Child↗

LIF, but not IL-6, regulates osteoprogenitor differentiation in rat calvaria cell cultures: modulation by dexamethasone.

Cytokines of the interleukin 6 (IL-6) subfamily are a group of factors produced by osteoblasts and acting through the same transducing element, membrane protein gp130. We have previously shown that exogenous (added to the culture medium) leukemia inhibitory factor (LIF) inhibits bone nodule formation and expression of osteoblast-associated genes in fetal rat calvaria (RC) cell cultures and that dexamethasone (Dex) increases the ID50 of LIF. To investigate the respective roles of IL-6-related cytokines and receptors in osteprogenitor differentiation, and their regulatory interplay with Dex, we used reverse transcribed polymerase chain reaction, bioassay, and blocking antibody techniques to assess the time courses of LIF, IL-6, LIF transmembrane receptor, IL-6 receptor, and gp130 expression in RC cell cultures grown with and without Dex. The levels of the mRNAs for IL-6, LIF, and gp130 decreased concomitantly with the formation of bone nodules. Dex treatment, which stimulates bone nodule formation, reduced the expression of LIF and IL-6 mRNAs and IL-6 bioactivity in the culture medium. LIF treatment strongly stimulated the expression of IL-6. Incubation with anti-LIF antibodies increased the number of nodules, while an antibody blocking IL-6 activity had little or no effect on nodule numbers and did not antagonize the action of exogenous LIF, indicating that IL-6 does not mediate the action of LIF in this system. Moreover, although exogenously added IL-6 was active in the cultures as noted by a reduction of nodule mineralization, it had no effect on nodule numbers, i.e., on osteoprogenitor differentiation, in the presence or absence of Dex. In conclusion, IL-6, LIF, and their receptors are expressed throughout the time-course of osteogenesis in RC cell cultures. However, only LIF, but not IL-6, appears to play a significant role in autocrine regulation of osteoblastic differentiation in this system. The antagonist action of Dex on the effects of exogenously added LIF, as well as the bone-promoting action of Dex in RC cell cultures, could be exerted partly through the down-regulation of the expression of endogenous LIF.

Animals↗

[Mifepristone in the treatment of 47 ectopic pregnancy patients].

OBJECTIVE: To investigate the effect and indication of mifepristone in treating ectopic pregnancy, 47 patients were divided into three groups. RESULTS: Twenty-nine cases were effective; 18 cases were ineffective and operated on in which we observed the gestational termination, bleeding capacity, and pathological changes in fallopian tube. We found that the effect was related to the drug dosage, levels of beta-hCG in blood and the operating time. CONCLUSION: High dosage of mifepristone in treating ectopic pregnancy is convenient, safe, and has no side-effects. It is suitable for patients with early ectopic pregnancy who have smooth life-sign, beta-hCG < 10 ng.ml-1, the mass in pelvic cavity < or = 5 cm, without acute belly-ache and pulsation of fetal heart in fallopian tube and who ask for the conservative treatment.

Abortifacient Agents, Steroidal↗

[Immunoprotection in guinea pigs using DNA recombinant plasmid rpDJt and expressed protein P68 in L. interrogans serovar lai].

Immunoprotection against the infection by Leptospira interrogans serogroup Icterohemorrhagiae serovar lai strain 017 was demonstrated in guinea pigs vaccinated with DNA recombinant plasmid rpDJt and expressed protein P68 derived from genomic library of Leptospira strain 017. Thirty days after active immunization, each group received intraperitoneally (1/2 dose) and subcutaneously (1/2 dose) inoculum of L. interrogans serovar lai stain 017; cultures were adjusted to 5 x 10(8) cells/ml. All guinea pigs were observed for 10 days after challenge. Survival (%) of P68 group was 100(7/7); P23 group was 75(3/4); group rpDJt was 77(10/13); group lack recombinant (control) pT7-7 was 25 (3/12), and group with whole-cell inactivated vaccine was 93(13/14). Although the protective antigen in the leptospires has yet to be determined, it is evident that expressed protein P68 conferred a high degree of immunoprotection in guinea pigs.

Animals↗

[Total cavo-pulmonary connection for complex congenital heart disease].

Between April 1994 and January 1997, 10 patients with complex congenital heart disease were treated with total cavo-pulmonary connection(TCPC). They included 7 males and 3 females, aged 2-17 years(mean 10.1 years). These cases were single ventricle in 5, tricuspid atresia in 4, severe Ebstein anomaly in 1. For construction of the right atrial lateral tunnel, Gore-Tex patch was used in 9 cases and autologous right atrial wall in another, 4 of the 10 patients underwent TCPC without aortic crossclamping. There were no operative deaths. The follow-up is 2-36 months(mean 12.3 months). All of these patients did well and were in NYHA class I. The advantages, operative indication and technique of TCPC and the experience of improvement of surgical results are briefly discussed in this paper.

Adolescent↗

[Study on hepatitis G virus infection in 63 posttransfusion patients with hematological diseases].

OBJECTIVE: To study the hepatitis G virus(HGV) infection in posttransfusion patients. METHODS: HGV RNA and HCV RNA were detected by RT-PCR, and anti-HGV and HBsAg were assayed by ELISA in 63 posttransfusion patients with blood diseases. RESULTS: The positive rates of HGV RNA, HCV RNA and anti-HGV were 7.9%, 46.0% and 6.3%, respectively. HGV infection was usually accompanied by HCV infection and elevation of ALT. CONCLUSION: HGV as well as HCV may transmitted by blood transfusion.

Flaviviridae↗