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Biomedical subjects

D Lu

Publications and source records attributed to D Lu.

At least 307 records · Page 17Linked to original sources

Chain-length dependence of lipid bilayer properties near the liquid crystal to gel phase transition.

The temperature dependence of the mean orientational order parameter in the vicinity of the liquid crystal to gel phase transition is obtained from the first moment M1 of deuterium nuclear magnetic resonance spectra for bilayers of chain perdeuterated phosphatidylcholines with acyl chains of 12, 14, 16, and 18 carbons. The data clearly show an increasing temperature dependence of the orientational order parameter in the vicinity of the transition, with the effect becoming more pronounced with decreasing chain length. Assuming a linear relationship between the mean orientational order parameter and the extension of the acyl chain, estimates of the change in area of the membrane at the transition are shown to be consistent with those obtained from other measurements. It is shown that the transition may be modeled in terms of a Landau expansion of the free energy involving a small number of phenomenological parameters. From this it is shown that the behavior of these systems in the temperature range of interest is, in large part, controlled by the close proximity of a spinodal to the transition temperature.

Biophysical Phenomena↗

Construction of a recombinant oral vaccine against Salmonella typhi and Salmonella typhimurium.

The viaB gene coding for the Vi antigen of Salmonella typhi Ty2 was subcloned into expression vector pYA248. The recombinant plasmid was termed SMM202 and transformed into Salmonella typhimurium chi 4072, an attenuated delta cya delta crp mutant. Recombinant S. typimurium Vi4072 had the ability to produce Vi capsular polysaccharide and also to invade and colonize the small intestine, mesenteric lymph nodes, and spleen of BALB/c mice. Mice orally immunized with Vi4072 developed serum and secretory antibody responses to the Vi antigen, as measured by a passive hemagglutination assay. Mice developed a delayed-type hypersensitivity following a footpad injection with Vi antigen after being sensitized orally with a suitable dose of Vi4072. Immunization of mice with Vi4072 afforded complete protection against fatal infection with virulent S. typhi Ty2. All data indicate that this route of antigen delivery is effective for stimulating antibody-mediated immunity and for inducing a cell-mediated immune response in BALB/c mice. Thus, S. typhimurium Vi4072 may serve as a vaccine for protection against typhoid fever and salmonellosis caused by S. typhimurium.

Administration, Oral↗

Protection from cold injury by deferoxamine, an iron chelator.

The presence of hydroxyl radical (OH) has been implicated in the pathogenesis of cold injury. Since iron is known to catalyze the OH formation responsible for cellular injury, this study was designed to examine whether an iron chelator such as deferoxamine can salvage a tissue from cold injury. Cold injury was induced in the hind limbs of rabbits. The experimental group received 0.6 mM of deferoxamine through the femoral vein prior to cooling of the limbs. Deferoxamine reduced the tissue injury, as evidenced by the decreased release of lactate dehydrogenase, a nonspecific marker for cellular injury. In addition, this drug inhibited OH formation and lipid peroxidation when examined by monitoring the formation of conjugated dienes and malonaldehyde, presumptive markers for lipid peroxidation. Rewarming of the cooled limbs was also associated with the loss of membrane phospholipids, with the corresponding accumulation of lysophosphoglycerides and free fatty acids, especially linoleic and arachidonic acids. Deferoxamine prevented the loss of phospholipids and inhibited the accumulation of amphipathic lipid products. These results indicates that deferoxamine salvaged the tissue from cold injury, possibly by preventing the formation of OH presumably by chelating iron, thus protecting the phospholipids from free radical attack.

Animals↗

Angiotensin-II induction of plasminogen activator inhibitor-1 gene expression in astroglial cells of normotensive and spontaneously hypertensive rat brain.

Angiotensin-II (AII) stimulates plasminogen activator inhibitor-1 (PAI-1) gene transcription, translation, and protein secretion from astroglial cells derived from normotensive [Wistar-Kyoto (WKY)] rat brain, an effect mediated by AII type 1 (AT1) receptors. Since abnormal expression of the brain AII system has been demonstrated in spontaneously hypertensive (SH) rats, we investigated the regulation of PAI-1 gene expression by AII in astroglial cells from the brains of these animals. AII caused an increase in PAI-1 gene expression in SH rat astroglia in a manner similar to that observed in WKY-derived cultures. However, both the basal and AII-stimulated levels of PAI-1 mRNA in SH rat astroglia were only 20% of those observed in WKY rat astroglial cultures. Consequently, there was a significant reduction in the de novo synthesis and secretion of PAI-1 from astroglia of SH rat brain. The reduced synthesis and secretion of PAI-1 from SH rat brain astroglia was associated with lower numbers of AT1 receptors in these cells. However, the steady state levels of AT1 receptor mRNA were comparable in both WKY and SH rat astroglia. This reduction in AII-modulated PAI-1 levels in SH rat astroglia is consistent with a proposed role of these interactions in the development of hypertension in these animals.

Angiotensin II↗

[The clinical relevant factors of the myocardial ischemic threshold].

The myocardial ischemic threshold (heart rate at the onset of ischemia) was assessed in 92 patients with coronary heart disease. The highest myocardial ischemic threshold (HMIT) ranged from 83 to 163 (122 +/- 18) beats/min usually happened during activities at the daytime. The lowest myocardial ischemic threshold (LMIT) ranged from 45 to 115 (82 +/- 17) beats/min usually happened when awaken early morning or asleep at night. The differences were statistically significant (P < 0.01). The mean variability of myocardial ischemic threshold (VMIT) was 30.22% (range from 8.2 to 51.2%). The variability was correlated positively with the number of ischemic episodes, negatively with LMIT, and larger in senior-aged group than in middle-aged group (P < 0.001). The authors suggest that LMIT and VMIT may be related to the severity of coronary lesions, coronary tonus, and the patients' prognosis, etc.

Age Factors↗

[Vibrio cholerae toxin B subunit gene expressed in a Salmonella vaccine strain].

This paper reports that the V. cholerae toxin B subunit (ctx B) gene was inserted into pYA 248 plasmid with the aspartate beta-semialdehyde dehydrogenase (asd)gene and the recombinant plasmid was transformed into S. typhimurium deleting asd gene. Results showed that ctx B gene was highly expressed and secreted into midium. This strain was able to colonize in the intestinal epithelium. Oral immunity and general immunity could produce antibodies at high level and enhance cellular immune responses. The animals orally inoculated with S. typhimurium x 4072 (pYA-ctx B) vaccine had remarkable protection against virulent V. cholear 569B strain and S. typhimurium strain. Use of such system provides useful method for oral vaccine.

Animals↗

[Chemical constituents of Rhodiola kirilowii (Reg.) Reg].

Three compounds were isolated from the water-soluble part of alcohol extracts of rhizomes of Rhodiola kirilowii. Two of them were identified as salidroside and tyrosol, respectively by chemical and spectral analysis. beta-sitosterol was obtained from the petroleum extracts of the plant.

Drugs, Chinese Herbal↗

[Study on pilules of indomethacin--PEG 6000].

Indomethacin (IDM)-PEG 6000 pilules were prepared using PEG 6000 as the carrier. The solubility of IDM in IDM-PEG 6000 pilules was about twice as much as pure IDM. When the effective dose of IDM-PEG 6000 was only half that of IDM tablet, the irritation of IDM-PEG 6000 pilule on rat stomach was reduced significantly but it still manifested the action of inhibiting the secretion of basal gastric acid.

Animals↗

Preconditioning of heart by repeated stunning. Adaptive modification of antioxidative defense system.

Previous studies demonstrated that preconditioning of a heart by repeated stunning can reduce the cellular injury to the heart from subsequent acute ischemic insult. To examine the possible biochemical mechanism for such myocardial preservation afforded by preconditioning, swine heart was subjected to four episodes of 5 min. stunning by occluding the left anterior descending coronary artery (LAD), followed by 10 min. of reperfusion after each stunning. Heart was then made regionally ischemic for 60 min. by LAD occlusion, followed by 6 hrs. reperfusion. Control heart was perfused for 60 min., followed by 60 min. ischemia and 6 hrs. reperfusion. The results of our studies indicated the stimulation of a number of antioxidative enzymes, including Mn-superoxide dismutase (Mn-SOD), catalase, glutathione peroxidase, and glutathione reductase, after repeated stunning and reperfusion. In addition, a number of new proteins were expressed after preconditioning the heart, including some oxidative-stress related proteins and 72 kDa heat-shock protein. These results suggest that preconditioning of a heart by repeated stunning may lead to strengthening of the oxidative defense system of the heart, which is likely to play a role in myocardial preservation during subsequent ischemic and reperfusion injury.

Adaptation, Physiological↗

Protection from nonfreezing cold injury by quinacrine, a phospholipase inhibitor.

A recent study from our laboratory indicated additional tissue injury during rewarming of a cooled rabbit leg. Oxygen-derived free radicals were believed to play a role in such "rewarming injury." Since free radicals may attack membrane phospholipids, we analyzed the phospholipid composition in the leg tissue during cooling and rewarming. Our results indicated significant breakdown of membrane phospholipids, particularly phosphatidylcholine and phosphatidylethanolamine, with a corresponding accumulation of lysophosphatidylcholine and nonesterified fatty acids. Quinacrine, a phospholipase inhibitor, was able to preserve membrane phospholipids during rewarming of the cooled leg. Rewarming of cooled tissue was also accompanied by additional tissue injury, as evidenced by the increased release of lactic acid dehydrogenase and creatine kinase, as well as enhanced lipid peroxidation, as evidenced by increased malonaldehyde formation. Quinacrine reduced the release of these intracellular enzymes and decreased lipid peroxidation, suggesting its efficacy as a therapeutic agent against hypothermic injury.

Animals↗

Alterations at the rel locus in human lymphoma.

The rel proto-oncogene has been mapped to chromosome region 2p11.2-14, a site associated with nonrandom rearrangements in non-Hodgkin's lymphoma. We have characterized an abnormal rel mRNA from a cell line derived from a diffuse large cell lymphoma, in which the evolutionarily conserved N-terminal half of the rel coding region was fused with the C-terminal coding region of an unrelated gene. In addition, rearrangement or amplification of the rel locus was found in the lymphomatous tissue of two follicular and one diffuse large cell lymphoma. The findings suggest involvement of rel in the pathogenesis of large cell lymphoma.

Amino Acid Sequence↗

Expression of firefly luciferase gene in Xenopus laevis oocyte.

Fusion plasmid pSV-Luc20 and pSV-Luc19 were constructed by using the larger BamHI restricted fragments of plasmid pDO432 containing the firefly luciferase (luc) gene and HindIII-BamHI restricted fragment of plasmid pSVK100 containing the SV-40 promoter as insert and vector, respectively. The fusion plasmid had different ligation orientations between the encoding sequence of luc gene and the SV-40 promoter, i.e., they were sense and antisense plasmid. When they were introduced into Xenopus oocyte by micro-injection, only pSV-Luc20 could be transcribed and translated into the enzymatic protein of luciferase with high biological activity. Therefore, firefly luciferase gene and Xenopus oocyte can be used as an excellent system for monitoring the activity of various promoters.

Animals↗

Full-length DQ beta cDNA sequences of HLA-DR2/DQw1 subtypes: genetic interactions between two DQ beta loci generate human class II HLA diversity.

Two-dimensional gel electrophoresis of DQ molecules from three different Dw subtypes (Dw2, Dw12, and Dw21/FJO) of the HLA-DR2/DQw1 haplotype reveals that one alpha beta heterodimer of DQ molecule is expressed by each subtype and the DQ beta chain is electrophoretically variable among the three DR2/DQw1 subtypes. We have constructed cDNA libraries from the same homozygous typing cells used in the two-dimensional polyacrylamide gel electrophoresis analyses (HTC VYT for Dw2, HTC DHO for Dw12, and HTC FJO for Dw21/FJO) and isolated DQ beta cDNA clones with full-length coding sequences for each subtype. The deduced amino acid sequences show that the DQ beta chains of these three DR2/DQw1 subtypes are highly polymorphic and confirm their electrophoretic heterogeneity: for a mature protein of 229 amino acids, they differ with each other by 10-17 amino acids in the first domain and by 3-7 residues in the C-terminal sequence. Comparison among the available DQ beta sequences representing the four major DQ specificities (DQw1, DQw2, DQw3, and DQw4) in the DQ subregion as defined by serologic method suggests that (1) DR2,Dw2,DQw1 and DR3,DQw2 haplotypes probably interact with each other to generate the DQw3 and DQw4 beta alleles and (2) an evolutionary scheme may be proposed to relate the various beta alleles of the four major DQ specificities.

Alleles↗

Method for identifying microbial antigens that stimulate specific lymphocyte responses: application to Salmonella.

Vaccine development and understanding of cellular immune stimulatory mechanisms have been impeded by the paucity of data on microbial antigens that stimulate protective immunity. We describe here a general method for identifying and isolating peptide antigens that specifically stimulate sensitized lymphocytes. First, Salmonella typhimurium C5 genomic DNA fragments were subcloned into Escherichia coli by use of the lambda gt11 expression vector. Next, antigens expressed by recombinant phage from this genomic library were tested for their capacity to stimulate proliferative responses in pooled lymphocytes obtained from BALB/c mice infected 14 days earlier with S. typhimurium. Of 2000 recombinant phages tested, 5 stimulated a polypeptide-antigen-specific proliferative response. Physical analyses of these 5 recombinant phages revealed cloned inserts of 0.5-2.4 kilobase pairs representing nonoverlapping regions of the C5 chromosome. Four of the five insert DNAs hybridized at high stringency to both S. typhimurium and Salmonella typhi total chromosomal DNA, suggesting that these pathogens of different host specificity share several antigenic determinants. Use of sensitized primary polyclonal lymphocytes provides a rapid and simple method for screening recombinant DNA libraries for clones that stimulate specific immune responses and avoids the use of cloned lymphocyte cell lines. This approach should be generally applicable to similar studies in different hosts of many other microbial pathogens.

Animals↗

[Demonstration of the presence of Methanobrevibacter in a colon cancer Chinese patient].

A fecal specimen from a Chinese patient (85-year-old man) suffering from colonic cancer was examined for the presence of methane-producing bacteria. As a result, a Methanobrevibacter organism was isolated. Our isolate did not grow in the presence of bile salts, a result different from Methanobrevibacter from healthy Americans' feces by Miller et al.

Aged↗