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Biomedical subjects

X Lu

Publications and source records attributed to X Lu.

At least 361 records · Page 20Linked to original sources
PubMed1997

[Studies on octanol-water partition coefficient and nasal drug absorption].

In order to find out the quantitative relationship between physicochemical properties of drugs and their nasal absorption, diltiazem hydrochloride and paracetamol were selected as model drugs and their octanol-water partition coefficient was determined. In situ nasal recirculation method at different pH values was used to estimate the rate constant of nasal drug absorption in rats. Results showed that quantitative relationship existed between partition coefficient and nasal absorption constant, with correlation coefficient being 0.9761(n = 9). Besides methods of partition coefficient determination, the in situ nasal recirculation manipulation was also improved.

Absorption↗
PubMed1997

[IR study on the thermal decomposition of trinuclear and tetranuclear iron benzoate complexes].

The title complexes shown as [Fe3O(C6H5COO)6(H2O)]Cl x 1.5H2O and [Fe4O2 (C6H5COO)7(bipy)2]ClO4 x 3.5H2O were prepared. Their thermal decomposition process was studied qualitatively and quantitatively by means of thermogravimetric analysis and infrared spectroscopic measurement of samples after heating at different temperatures. From the experimental results, the possible thermal decomposition process of the two compounds can be deduced. Additionally, according to the fact that the nu(as) (COO) of the two compounds decreases while the nu(s) (COO) remains unchanged as the heating temperature increases. It can be drawn that the carboxylate coordinative form possible change from bridged to chelate one.

English Abstract↗
PubMed1997

Correlative studies of MR findings with neuropathology in Shy-Drager syndrome and striatonigral degeneration.

OBJECTIVE: To determine the pathologic bases of the abnormal signal intensities detected on magnetic resonance imaging (MRI) in Shy-Drager syndrome (SDS) and striatonigral degeneration (SND). METHODS: The correlation of MRI and pathological findings was prospectively evaluated by postmortem scanning of the brain in a case of SDS and another of SND. MRI was performed by using a 1.0 T superconductive magnetic unit, with spin echo (SE) pulse sequences. The brain sections were prepared parallel to the MRI planes. The gross and microscopic pathological studies were conducted according to the corresponding abnormal signal intensities on MRI. RESULTS: In SDS, abnormal hypointense signals on T2 weighted MR images were symmetrically demonstrated in bilateral putamen, where a remarkable positive Prussian blue stain reaction was revealed on pathological examinations. In SND, MRI showed isointense signals on T1 weighted images and hyperintense signals on T2 weighted images in bilateral putamen, and the microscopic findings included necrosis, abundant reactive fibrillary astrocytes and prominence of capillary vascular networks, as well as marked lipofuscin. The number of neurons decreased in both cases. CONCLUSIONS: The demonstration of the abnormal signals in the putamen on MRI is of important value in establishing an antemortem diagnosis of SDS and SND.

Female↗
PubMed1997

[Effect of dynorphin A1-13 on hypoxia-ischemic brain injury in neonatal rats].

OBJECTIVES: To study the secondary pathological changes in the central nervous system after injury and the role of dynorphin A1-13 in hypoxi-ischemic brain injury in neonatal rats. METHODS: Changes of concentrations of dynorphin A1-13 immunoreactives in some brain areas at different times after brain injury and the effect of injecting 8 microliters dynorphin A1-13 anti-serum into the medulla pool on pathological process of brain injury were observed in perinatal cerebral hypoxia ischemic rat models prepared by permanent ligation of right common carotid artery combined with a temporary systematic hypoxia at 37 degrees C in 7 day old Wistar rats. RESULTS: Concentrations of dynorphin A1-13 in cortex, hypothalamus and hippocampus increased significantly after the injury. Microinjection of anti-dynorphin A1-13 serum into the medulla pool 1 h preinjury might markedly reduce brain edema and improve the physiological condition. CONCLUSIONS: Dynorphin A1-13 plays a role in the pathophysiological process of brain hypoxia-ischemia and excessive amount of dynorphin A1-13 had some detrimental effect on the process.

Animals↗
PubMed1997

[The use of platysmal myocutaneous flaps in laryngeal reconstruction].

Vertical frontal subtotal laryngectomy, a procedure that can remove as much as 90% of the larynx, was used to produce a functionally acceptable neolarynx with platysmal myocutaneous flaps. Thirty-two patients with laryngeal carcinoma underwent this operation. All flaps survived and there was no necrosis after operation. With the exception of one patient who require nasal feeding because of an irritating cough when swallowing food, all the other patients regain breathing, swallowing and phonating of laryngeal function. The operative methods, advantages and experiences are discussed in this paper.

Adult↗
PubMed1997

[Three-dimensional reconstruction of sinusoids from serial sections].

The three-dimensional image of sinusoids has been reconstructed by computer image processing using a new method of registration. By observing the reconstructed image of sinusoids, we can easily understand the anatomy of sinusoids. Theoretical analysis and experimental results suggest that the method is feasible and practicable.

Animals↗
PubMed1996

CDC42 and Rac1 are implicated in the activation of the Nef-associated kinase and replication of HIV-1.

BACKGROUND: The negative factor (Nef) of human and simian immunodeficiency viruses (HIV-1, HIV-2 and SIV) is required for high levels of viremia and progression to AIDS. Additionally, Nef leads to cellular activation, increased viral infectivity and decreased expression of CD4 on the cell surface. Previously, we and others demonstrated that Nef associates with a cellular serine kinase (NAK) activity. Recently, it was demonstrated that NAK bears structural and functional similarity to p21-activated kinases (PAKs). RESULTS: In this study, we demonstrate that Nef not only binds to but also activates NAK via the small GTPases CDC42 and Rac1. First, the dominant-negative PAK (PAKR), via its GTPase-binding domain, and dominant-negative GTPases (CDC42Hs-N17 and Rac1-N17) block the ability of Nef to associate with and activate NAK. Second, constitutively active small GTPases (CDC42Hs-V12 and Rac1-V12) potentiate the effects of Nef. Third, interactions between Nef and NAK result in several cellular effector functions, such as activation of the serum-response pathway. And finally, PAKR, CDC42Hs-N17 and Rac1-N17 decrease levels of HIV-1 production to those of virus from which the nef gene is deleted. CONCLUSIONS: By activating NAK via small GTPases and their downstream effectors, Nef interacts with regulatory pathways required for cell growth, cytoskeletal rearrangement and endocytosis. Thus, NAK could participate in the budding of new virions, the modification of viral proteins and the increased endocytosis of surface molecules such as CD4. Moreover, blocking the activity of these GTPases could lead to new therapeutic interventions against AIDS.

3T3 Cells↗
PubMed1996

Myoblast gene therapy in canine mucopolysaccharidosis. I: Abrogation by an immune response to alpha-L-iduronidase.

Three dogs with deficiency of the lysosomal enzyme alpha-L-iduronidase were treated by gene replacement therapy targeted at muscle. Direct intramuscular injections of plasmid encoding the alpha-L-iduronidase gene cDNA resulted in no detectable enzyme production, but may have resulted in immunologic sensitization to iduronidase protein, which the dogs lack totally. Myoblasts were grown from skeletal muscle biopsies and transduced with a retroviral vector containing the canine gene under control of the muscle creatine kinase enhancer. Several hundred-fold overexpression of enzyme production occurred in cultured cells; however, following reintroduction of the cultured cells into dogs, enzyme production declined rapidly. Concurrent with the falling enzyme levels, there was production of specific immunoglobulin G (IgG) antibody against iduronidase that was further associated with cellular infiltration of the myoblast injection sites. Most inflammatory cells were lymphocytes and plasma cells, suggesting local humoral and cellular immune responses to the enzyme-producing muscle cells. PCR analysis of tissues collected 2-22 weeks after the final treatment showed the persistence of Neo and canine alpha-L-iduronidase sequences in a progressively decreasing percentage of myoblasts. Results from this study in a canine model of mucopolysaccharidosis I underscore the fact that immunologic reactions to cells producing desirable, normal, but foreign, proteins may be as much an impediment to gene therapy as reactions to the viral vectors used to introduce the foreign gene.

Animals↗
PubMed1996

Effect of up-regulation of NMDA receptors on cerebral O2 consumption and blood flow in rat.

We tested the hypothesis that cerebrocortical blood flow and O2 consumption would be proportional to an up-regulated number of functional N-methyl-D-aspartate (NMDA) receptors. Previous work had shown a relationship between cerebral metabolism and NMDA receptor activity. We increased the specific binding to NMDA receptors in the cerebral cortex, from 2.2 +/- 0.9 to 4.5 +/- 0.8 (density units) in male Long-Evans rats by daily giving two intraperiotoneal injections (30 mg/kg) of CGS-19755, an NMDA receptor inhibitor, for 7 consecutive days (discontinued for 20 h before experiment). Twelve up-regulated (CGS treated) and 12 control rats were used in this study. Under isoflurane anesthesia and after topical stimulation of the right cerebral cortex with 10(-2) M NMDA, the blood flow (14C-iodoantipyrine method) increased from 98 +/- 11 ml/min/100 g in the unstimulated cortex of the control rats to 161 +/- 37 ml/min/100 g in the stimulated cortex. The unstimulated value for blood flow (95 +/- 7 ml/min/100 g) did not change in the upregulated group but it doubled (194 +/- 69 ml/min/100 g) in the stimulated, upregulated cortex. Similarly, O2 consumption (cryomicrospectrophotometrically determined) in normal rats increased 46%, from 9.3 +/- 1 ml/min/100 g to 13.6 +/- 4 after NMDA stimulation. While in the upregulated animals, O2 consumption increased 103% from 7.9 +/- 0.6 to 16 +/- 6.5 after NMDA stimulation. In conclusion, NMDA receptor upregulation does not alter basal cerebrocortical blood flow or O2 consumption but in the NMDA-stimulated cortex, the blood flow and O2 consumption increase is dependent on the number of NMDA receptors present.

Animals↗
PubMed1996

Intracellular and in vitro-translated 27-kDa proteins contain the 3C-like proteinase activity of the coronavirus MHV-A59.

The coronavirus mouse hepatitis virus-A59 (MHV-A59) encodes a serine-like proteinase (3C-like proteinase or 3CLpro) in ORF 1a of gene 1 between nucleotides 10,209 and 11,114. We previously have demonstrated that proteins expressed in vitro from a cDNA clone of the 3CLpro region possess proteinase activity, and that the proteinase is able to cleave substrate in trans. We sought to determine if the 27-kDa in vitro cleavage product (p27) was an active form of the 3CLpro and whether this was consistent with the 3CLpro expressed in virus-infected cells. Antibodies directed against the 3CLpro domain detected 27-kDa MHV proteins in vitro and in MHV-A59-infected cells. The 27-kDa proteins were able to cleave substrate in trans without other protein cofactors or supplemental membranes, and the p27 proteinase activity was retained after purification by immunoprecipitation and gel electrophoresis. When p27 was expressed in vitro with portions of the amino-and carboxy-terminal flanking domains (MP1 and MP2), p27 was not liberated by cls cleavage. The proteolytic activity of the 27-kDa proteins was inhibited by a variety of cysteine and serine proteinase inhibitors, and was eliminated by the cysteine proteinase inhibitor E64d. These results indicate that the 27-kDa protein is a mature proteinase in MHV-A59-infected cells, and that appropriate processing of this molecule occurs in vitro.

Amino Acid Sequence↗
PubMed1996

1-O-octadecyl-2-O-methyl-glycerophosphocholine inhibits the transduction of growth signals via the MAPK cascade in cultured MCF-7 cells.

1-O-Octadecyl-2-O-methyl-glycerophosphocholine (ET18-OCH3) is an ether lipid with selective antiproliferative properties whose mechanism of action is still unresolved. We hypothesized that since ET18-OCH3 affects a wide variety of cells, its mechanism of action was likely to involve the inhibition of a common widely used pathway for transducing growth signals such as the mitogen-activated protein kinase (MAPK) cascade. To test this, we established conditions whereby quiescent MCF-7 cells took up ET18-OCH3 in sufficient quantities that inhibited cell proliferation subsequent to the addition of growth medium and examined the activation of components of the MAPK cascade under these conditions. ET18-OCH3 inhibited the sustained phosphorylation of MAPK resulting in a decrease in the magnitude and duration of activation of MAPK in cells stimulated with serum or EGF. ET18-OCH3 had no effect on the binding of EGF to its receptors, their activation, or p21ras activation. However, an interference in the association of Raf-1 with membranes and a resultant decrease in Raf-1 kinase activity in membranes of ET18-OCH3-treated cells was observed. ET18-OCH3 had no direct effect on MAPK or Raf-1 kinase activity. A direct correlation between ET18-OCH3 accumulation, inhibition of cell proliferation, Raf association with the membrane, and MAPK activation was also established. These results suggest that inhibition of the MAPK cascade by ET18-OCH3 as a result of its effect on Raf-1 activation may be an important mechanism by which ET18-OCH3 inhibits cell proliferation.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1996

Discordance between accumulated p53 protein level and its transcriptional activity in response to u.v. radiation.

In response to DNA damage, the transcriptional activity of p53 rises. This has been thought to be due to an increase in the level of p53 protein. By comparing the p53 protein level and its ability to transactivate target genes Waf1/Cip1 and mdm2 in both T22 and NIH3T3 cells irradiated with u.v., a discordance between the p53 protein level and its transcriptional activity was observed. When the cells were irradiated with 10 J/m2 of u.v., there was a substantial increase in expression of Waf1/ Cip1 and mdm2. However, little increase in Waf1/Cip1 and mdm2 expression was observed in T22 and NIH3T3 cells 8 or 9 h after exposure to 50 J/m2 of u.v., although the p53 protein level accumulated to its highest level under these conditions. Interestingly, a significant increase in Waf1/Cip1 expression was seen 24 h after irradiation in NIH3T3 cells, indicating that the inhibition of p53 transcriptional activity is reversible. Discordance between the transcriptional activity of p53 and its protein level was further studied using a cell line expressing the p53 reporter plasmid RGC delta fosLacZ. Using double immunofluorescence staining, the coexpression of p53 and beta-galactosidase from the reporter plasmid in the same cells was investigated. The observed lack of correlation between the elevated p53 and beta-galactosidase and expression in u.v. irradiated cells strongly indicates that the ability of p53 to transactivate its target genes is not simply correlated to its protein level. The results indicate that the transcriptional activity of p53 may be negatively regulated.

3T3 Cells↗
PubMed1996

Molecular cloning of MADM: a catalytically active mammalian disintegrin-metalloprotease expressed in various cell types.

A peptide sequence of a metalloprotease purified from bovine brain [Chantry, Gregson and Glynn (1989) J. Biol. Chem. 264, 21603-21607] was used to design an oligonucleotide probe for screening a bovine brain cDNA library. A contig of the two overlapping cDNA clones that were isolated encoded a 748-amino-acid polypeptide with similarity to the disintegrin-metalloprotease precursor proteins of haemorrhagic snake venom. The bovine protein has been named MADM, for mammalian disintegrin-metalloprotease. The predicted mature protein has 534 amino acids arrayed as extracellular metallo-protease and disintegrin (potential integrin-binding) domains, a transmembrane helix and a basic/proline-rich cytoplasmic C-terminus. Highly conserved homologues of bovine MADM were found in cDNA libraries of rat brain and a human U937 histiocytic lymphoma cell line. A wide variety of mammalian cell lines expressed low levels of MADM mRNA (4.5 and 3.2 kb transcripts) and mature polypeptide (M(r) 62000), as assessed by Northern analysis and Western blotting with an antiserum raised to a peptide within the disintegrin domain. MADM appears to be a rather distantly related member of the reprolysin protein family, which includes both the snake venom disintegrin-metalloproteases and a number of predicted cell-surface disintegrin-containing mammalian proteins.

Amino Acid Sequence↗