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Biomedical subjects

M Liu

Publications and source records attributed to M Liu.

At least 505 records · Page 28Linked to original sources

UV-B/A irradiation of mouse keratinocytes results in p53-mediated WAF1/CIP1 expression.

The tumor suppressor gene p53 is involved in controlling cell cycle checkpoint or triggering apoptosis. p53 may accomplish these roles by acting as a sequence-specific transcription factor. One of the downstream targets of p53 transcription control is the WAF1/CIP1 gene, whose gene product p21 interacts with several cyclins and cyclin-dependent kinases, resulting in inhibition of these kinases. In our previous studies, we have shown that the p53 protein level in mouse keratinocytes was elevated following UV-B/A irradiation. In this paper we further investigated the consequences of increased p53 protein level by characterizing p53 DNA-binding level and WAF1/CIP1 gene expression in UV-B/A-irradiated mouse keratinocytes. Consistent with the increased level of p53 protein, both p53 DNA-binding level and steady-state level of WAF1/CIP1 mRNA were elevated. We have demonstrated that the induction of WAF1/CIP1 mRNA was mediated by p53, since no WAF1/CIP1 induction was observed in p53-deficient cells upon UV-B exposure. These observations suggest an important role for the tumor suppressor gene p53 in the response of keratinocytes to the biologically relevant UV-B/A irradiation and in suppressing UV-induced skin cancer.

Animals↗

Mario Liu replies.

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Journal Article↗

Definition of a lamina propria T cell responsive state. Enhanced cytokine responsiveness of T cells stimulated through the CD2 pathway.

This study was designed to compare cytokine release in lamina propria lymphocytes (LPLs) and PBLs activated by Abs against CD3, CD2, and CD28. LPL T cells were significantly more responsive to CD2 ligation than PBL, as determined by release of IFN-gamma, IL-2, IL-4, and TNF-alpha. Moreover, CD28 co-ligation in LPLs exaggerated CD2 > CD3 dominance in cytokine induction. PHA-activated PBLs expressed more CD2 receptors than freshly isolated LPLs, but were less responsive to activation through CD2, indicating that postreceptor pathways in LPL may be adapted specifically to facilitate CD2-mediated cytokine secretion. Antiphosphotyrosine (APT) immunoblotting revealed inducible substrate phosphorylation during CD2, but not CD3, ligation in whole LPLs, as well as LPL-derived T cell lines. PBLs cocultured with an irradiated B cell line, Daudi, and IL-2 for 5 days attained a CD2-dominant cytokine-secretion pattern with identical tyrosine phosphorylation profiles as freshly isolated LPL or LPL T cell lines. PHA-activated PBLs did not produce these tyrosine phosphorylation profiles. This suggests that B lymphocytes in the lamina propria may contribute to a T cell differentiation process in which CD2, possibly by potentiation of its postreceptor pathway, becomes a prominent receptor for induction of cytokine secretion.

Animals↗

The effect of mechanical strain on fetal rat lung cell proliferation: comparison of two- and three-dimensional culture systems.

Normal growth of the fetal lung is dependent on fetal breathing movements. We have previously reported that an intermittent strain, which simulates normal fetal breathing movements, stimulates DNA synthesis and cell division of mixed fetal rat lung cells maintained in organotypic culture. To examine which cell type is responding to mechanical strain and to investigate whether the effects of strain on cell proliferation and mechanotransduction are affected by tissue architecture, we isolated fetal lung cells and subjected them to intermittent strain either as two-dimensional monolayer cultures or as three-dimensional organotypic cultures. Strain enhanced DNA synthesis of mixed cells, epithelial cells, and fibroblasts when cultured in a three-dimensional configuration. In contrast, no stimulatory effect on cell proliferation was observed when cells were strained as monolayer cultures. Intracellular signals, induced by strain, and cell morphology also varied depending on the culture conditions. These results suggest that mechanical strain stimulates the proliferation of both epithelial cells and fibroblasts and that the response of fetal lung cells to mechanical strain in vitro depends on cellular architecture.

Animals↗

Blunt gastrointestinal injury in trauma patients.

The evaluation, management, and final outcome of 34 patients with blunt gastrointestinal injury (BGI) were reviewed. Initial absence of symptoms and signs led to two delayed diagnoses. Sonography provided 80% (12/15) positive-predictive value, and three false-negative patients were subsequently detected by diagnostic peritoneal lavage (DPL). Besides repeated clinical surveillance, screening by sonography complemented with DPL provided early detection of blunt bowel injury in trauma patients. In the outcome analysis, BGI patients with high injury-severity scores, intraoperative hypotension, or accompanying major medical diseases were associated significantly with increased risk of infectious complications (P < .05).

Adolescent↗

Cloning the rat homolog of the CD28/CTLA-4-ligand B7-1: structural and functional analysis.

T cell activation involves the delivery of two independent signals to the naive T cell. The first signal occurs with engagement of the TCR. One of the best characterized second signals is ligation of CD28 on the surface of T cells by B7 molecules (B7-1, B7-2) present on the surface of activated antigen presenting cells (APCs). Recent studies have demonstrated that injection of a human fusion protein, CTLA-4-Ig, which in humans binds to both B7-1 and B7-2, prevents cardiac allograft rejection in a rat transplantation model when given 48 h after engraftment. In order to better characterize the role of B7-1 (which is maximally expressed 48 h after activation of APCs) in this model, as well as in models of tumor-induced immune responses, we have cloned the rat homolog of B7-1, and now report on its structure and function. A 1030 bp cDNA containing the entire coding sequence of the rat B7-1 was cloned with a polymerase chain reaction strategy utilizing degenerate primers derived from published murine and human B7-1 sequences. The rat B7-1 coding sequence is 67 and 81% homologous to human and murine B7-1 cDNAs, and the predicted peptide sequence is likewise 57 and 66% identical to the peptide sequences of human and murine B7-1 respectively. The greatest area of identity occurs in the extracellular portion of the molecule, particularly the Ig-C like domain.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Early repair of traumatic ventricular septal defect and mitral valve regurgitation.

Traumatic ventricular septal defect with valvular injury is an uncommon blunt trauma. It may develop either immediately or be delayed, but it should be corrected electively. With hemodynamic instability and cardiopulmonary deterioration, however, early repair is necessary as a lifesaving procedure. Two-dimensional echocardiography and Doppler color flow mapping are very important for rapid detection in patients who are critically injured. This is a case report of the successful repair of ventricular septal defect and posterior leaflet disruption of mitral valve right after blunt trauma.

Adult↗

Surfactant dysfunction develops when the immunized guinea-pig is challenged with ovalbumin aerosol.

BACKGROUND: The cause of the airway resistance developing during an asthma attack is not completely understood. Besides bronchospasm and airway oedema a surfactant dysfunction has been suggested as a reason for an increased airway resistance. OBJECTIVE: This paper aims at examining if indeed surfactant dysfunction develops when an asthma attack is induced in guinea-pigs. METHODS: Guinea-pigs, immunized against ovalbumin and then challenged (by inhaling the antigen) underwent lung function tests (n = 7) and were compared with seven animals challenged, but not immunized. Lung lavage was carried out in three groups of guinea-pigs: controls, never immunized nor challenged (n = 7), not immunized but challenged (n = 6), immunized and challenged, no lung function test (n = 6). After concentrating the lavage fluid 10 times the surface activity was evaluated with the pulsating bubble surfactometer. The fluid's concentration of phospholipids and proteins was determined as was the phospholipid composition. RESULTS: The 19 immunized and challenged animals all developed severe respiratory distress, six so seriously that they died. Lung function tests showed significantly increased airway resistance and decreased tidal volume, minute volume, and dynamic compliance. Surface activity of lavage fluid from immunized and challenged animals was significantly reduced when compared with fluid from control animals (P < 0.01). Immunization and challenge had no effect on the lavage fluid's phospholipid concentration or composition, but the proteins were at a higher concentration than in the fluid of the controls (P < 0.01). CONCLUSION: Proteins leaking into the airways inhibited the surfactant. This, in turn might have caused conducting airways to become blocked by liquid columns, which would increase airway resistance.

Administration, Inhalation↗

Mechanical strain-enhanced fetal lung cell proliferation is mediated by phospholipase C and D and protein kinase C.

The signaling pathways by which intermittent strain (60 cycles/min, 15 min/h) regulates proliferation of mixed fetal rat lung cell in vitro have been investigated. Adenosine 3',5'-cyclic monophosphate (cAMP) content and cAMP-dependent protein kinase (PKA) activity were not affected by strain. The stimulatory effect of strain on DNA synthesis was also not influenced by the cyclic nucleotide-dependent protein kinase inhibitors H-8 or HA-1004, the adenylate cyclase inhibitor SQ-22536, or a PKA inhibitor and cAMP antagonist, adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS). In contrast, intracellular concentrations of two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), were dramatically increased after a short period of strain. This increase in second messengers was accompanied by an increased tyrosine phosphorylation of phospholipase C-gamma 1. Phospholipase D activity was also increased by strain. Mechanical strain elicited a shift in the subcellular distribution of PKC activity from cytosol to membranes shortly after the onset of strain. The specific activity of PKC in the membranes increased 6- to 10-fold within 5-15 min and remained increased throughout a 48-h period of intermittent strain. Strain-induced PKC activation and DNA synthesis were blocked by the PKC inhibitors H-7, staurosporine, and calphostin C, as well as by the phospholipase C inhibitor U-73,122. We conclude that mechanical strain of mixed fetal rat lung cells activates phospholipid turnover via phospholipases, followed by PKC activation, which then triggers the downstream events that lead to cell proliferation.

Animals↗

Antisense oligonucleotides for PDGF-B and its receptor inhibit mechanical strain-induced fetal lung cell growth.

An intermittent mechanical strain regimen, which simulates fetal breathing movements, has been shown to enhance DNA synthesis and cell division of fetal rat lung cells. The signaling mechanism through which the physical stimulus is transduced is unknown. Herein, we report that mechanical strain (5% elongation, 60 cycles/min) of fetal lung cells, cultured in a three-dimensional environment provided by Gelfoam sponges, increased the mRNA levels of platelet-derived growth factor B (PDGF-B) and beta-receptor (PDGF-beta-R) within 5 min of the onset of strain. Both PDGF-BB and PDGF-beta-R proteins were increased after a 24-h intermittent strain (15 min/h). Phosphorothioate antisense PDGF-B oligonucleotides (ON) at 15 microM abolished the strain-enhanced DNA synthesis and cell growth. Scrambled PDGF-B ON had no such effect. A neutralizing PDGF-BB antibody (10 micrograms/ml) also attenuated strain-induced DNA synthesis. Furthermore, the strain-induced stimulatory effect on DNA synthesis of fetal lung cells was blocked by tyrphostin 9 (1 microM), a PDGF receptor-associated tyrosine kinase inhibitor, but not by its inactive structural analogue tyrphostin 1. Antisense but not sense PDGF-beta-R ON (10 microM) also abrogated the strain-enhanced DNA synthesis. These results suggest that physical forces such as fetal breathing movements regulate fetal lung cell growth by controlling PDGF-B and PDGF-beta-R gene expression.

Animals↗

Antioxidant activity of Chinese ant extract preparations.

Chinese ant extract preparations (CAEP) are a Chinese traditional medicine which is mainly used as a health food or drink for the treatment of rheumatism, rheumatoid arthritis, chronic hepatitis, sexual hypofunction, and antiaging in China. The effects on free radicals were examined by electron spin resonance spectrometry using the spin trapping agent 5.5-dimethyl-1-pyrroline-1-oxide (DMPO). Superoxide radicals (3.35 x 10(15) spins/ml) were quenched 50% by the extract at 0.5 mg/ml. The CAEP extract at 0.7 mg/ml inhibited 50% of hydroxyl radicals (52.0 x 10(15) spins/ml) generated by the Fenton reaction. Against DPPH radical, the scavenging action of CAEP was observed at 1.8 mg/ml of the extract and 50% of the DPPH radicals (8.14 x 10(15) spins/ml) were quenched. In vitro tests showed that CAEP inhibited the production of thiobarbituric acid-reactive substances, an index of lipid peroxidation, in rat brain homogenate.

Animals↗

Antitumor effect of keto-diepoxides isolated from the fungus Nattrassia mangiferae.

A novel keto-diepoxide Sch 49209 and its derivative Sch 50672, produced by the fungus Nattrassia mangiferae, inhibited tumor cell invasion through an artificial basement membrane. These compounds, at nontoxic concentrations, inhibited invasion of HT-1080 cells in a dose-dependent manner. The IC50 values for Sch 49209 and Sch 50672 were 0.75 and 8 microM, respectively, when cells were incubated with drugs for 5 h. Sch 49209 inhibited both tumor cell invasion and cell motility to the same extent under conditions that did not cause any apparent cytotoxicity. Sch 4209 and Sch 50672, however, inhibited the growth of ras-transformed cells in a semisolid medium in a 5-day culture with IC50 values of 0.6 and 2.4 microM, respectively. They also inhibited the anchorage-dependent growth of pT24 cells in vitro with IC50 values of 0.5 and 0.9 microM for Sch 40209 and Sch 50672, respectively. Using the murine lung epidermoid carcinoma M27 cells implanted SC in mice as a model, we found both Sch 49209 and Sch 50672 inhibited the growth of this tumor at doses ranging from 2 to 10 mg/kg. These compounds also decreased the formation of spontaneous lung metastasis in this model. Sch 50672 inhibited the growth of human tumor xenografts, SW620 and A431, in athymic mode mice. Our data suggest that keto-diepoxides inhibit tumor growth and metastasis and that this activity may be due, in part, to anti-invasive activity.

Animals↗

Emergency surgical intervention for severe corrosive injuries of the upper digestive tract.

BACKGROUND: In treating severe corrosive injury of the esophagus and stomach, prompt diagnosis, adequate fluid resuscitation and warranted surgical intervention are the most important factors in rescue of critically ill patients. The purpose of this study was to evaluate the need for, and the advantages of, a surgical approach to treatment of such corrosive injuries to the upper gastrointestinal (UGI) tract, as well as to select the most suitable technique to achieve a good survival rate. METHODS: From January 1983 to December 1991, 220 patients were treated for caustic ingestion injury to the UGI tract. A retrospective review of their records allowed targeting of 27 patients with severe corrosive injury that surgical intervention was required. In this study, peritoneal sign was taken as the key indicator for early emergency operation. The age, sex, elapsed time from injury to operation, the sort and quantity of caustic agent used, injury mechanism, clinical manifestations, alternative surgical treatment methods and causes of death were also reviewed and analyzed in this study. RESULTS: The patients included 13 men and 14 women, of whom the majority were adults (96.3%) who had attempted suicide (85.2%). All of them had taken liquid corrosive agents, usually hydrochloric acid (63%). Eighteen underwent emergency operations; the other nine received only supportive treatment, given their terminal status. The mortality rates for patients with surgery and supportive treatment were 66.7% and 100%, respectively. Four patients died after undergoing esophagectomy with resection of the stomach using the thoracoabdominal method. Only three of the eight patients who received esophageal stripping combined with resection of the stomach through the abdomen died (37.5%). CONCLUSIONS: The time elapsed between injury and development of peritoneal sign is a good indicator of the severity and extent of the injury. When peritoneal sign manifests at a very early stage, it is an indicator that the corrosive injury is very advanced in its progress and that, no matter what procedures were performed, the outcome would be the same. Yet if there were a six-hour gap then aggressive surgical management can rescue some patients. It is recommended based on experience here, that when using the surgical approach, resection of the stomach with stripping of the esophagus is superior to the thoracoabdominal method.

Adolescent↗

Anomalous origin of left coronary artery from pulmonary artery. Successful correction for a 7-year-old patient.

A 7-year-old girl with an anomalous origin of the left coronary artery from the pulmonary artery restored connection of the left coronary artery to the ascending aorta by aortocoronary bypass graft. Aortocoronary bypass grafting was performed with a vascular prosthesis. Postoperative angiography showed a patent left coronary artery without narrowing or kinking. Clinical improvement was rapid and the left ventricular function recovered completely.

Child↗

Effects of ginsenoside Rb1 and Rg1 on synaptosomal free calcium level, ATPase and calmodulin in rat hippocampus.

Calcium homeostasis in synaptosomes is altered during aging. The intrasynaptomal free calcium concentration ([Ca2+]i) was determined in 3- and 24-month-old rats treated with or without Rb1 and Rg1. As expected, the [Ca2+]i level increased with age. Treatment with Rbl and Rgl elicited an obvious decrease of [Ca2+]i content, especially in aged rates. In addition, Rb1 and Rgl significantly stimulated the activity of Na+, K+-ATPase while Rbl inhibited the activity of Ca2+, Mg2+-ATPase and calmodulin. In view of the close relationship of [Ca2+]i level with aging, the changes of [Ca2+]i induced by Rbl and Rgl, as shown by our results, might provide an explanation of the mechanisms of their antiaging function.

Aging↗