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Biomedical subjects

S Lu

Publications and source records attributed to S Lu.

At least 361 records · Page 20Linked to original sources

Biophysical mechanism of the scavenger site near T cell-presented epitopes.

We seek to identify consensus sequences in digested fragments of antigenic proteins regulating selection and major histocompatibility complex (MHC)-restricted presentation to T cells of epitopes within those fragments. One such pattern, of recurrent, hydrophobic sidechains forming a longitudinal hydrophobic strip when a sequence is coiled as an alpha-helix, is found in or near most T cell-presented epitopes. Such recurrent hydrophobicity may lead to protease-protected coiling of the fragment against endosomal membranes and transfer to MHC molecules. This concept leads to better identification of T cell-presented sequences and possible to engineering of T cell-presented vaccines to affect their potency and MHC restriction.

Amino Acid Sequence↗

Genetic mapping of a new homeobox gene to mouse chromosome 7.

A newly identified homeobox gene designated Dbx has been mapped to mouse Chromosome (Chr) 7. This gene is expressed in a restricted manner in developing mouse brain and spinal cord and has amino acid sequence similarities with members of the homeobox gene family such as Drosophila H2.0 and mouse Hlx. Using a fragment of the Dbx cDNA as a probe, a PstI restriction fragment length polymorphism was used to determine genotypes of 144 progeny from an interspecific backcross. Segregation analysis revealed linkage of Dbx with six prepositioned reference loci on mouse Chr 7. No recombination was observed between Dbx and Odc-rs6, indicating that Dbx lies approximately 25 cM distal to the Chr 7 centromere in a region that has conserved linkage relationships with regions of human Chrs 11 and 19.

Animals↗

Human immunodeficiency virus type 1 entry into T cells: more-rapid escape from an anti-V3 loop than from an antireceptor antibody.

The entry of human immunodeficiency virus type 1 into two T-cell lines has been analyzed to determine the relative time courses with which virus entry can be blocked (i) by washing, (ii) by adding a monoclonal antibody to the V3 loop of gp120 that neutralizes without blocking CD4 binding (0.5 beta), or (iii) by adding an antireceptor monoclonal antibody that competes for virus binding (leu3a). During entry into C8166 cells, 50% escape from the wash as well as the anti-V3 loop antibody required 20 min, whereas 50% escape from the leu3a block required 45 minutes. In contrast, during entry into H9 cells, 50% escape from the wash block required 50 min, 50% escape from the anti-V3 loop antibody required 110 min, and 50% escape from the antireceptor antibody required 190 min. These results demonstrate that the times required for entering virus to escape each of the blocks were cell type specific. They also demonstrate that V3 loop-dependent steps occur relatively early in entry and suggest that binding of gp120 to CD4 is important for late as well as early steps in human immunodeficiency virus type 1 entry.

Antibodies, Monoclonal↗

Nitric oxide as a putative nonadrenergic noncholinergic inhibitory transmitter in the canine pylorus in vivo.

Antropyloroduodenal motility was recorded in seven anesthetized dogs to assess the role of nitric oxide and L-arginine metabolites in nonadrenergic noncholinergic (NANC) mediation of pyloric relaxation. Pyloric activity induced by duodenal field stimulation was inhibited by antral field stimulation and electrical vagal stimulation. Intra-arterial NG-L-arginine-methyl-ester (L-NAME) reduced the inhibition from antral or vagal stimulation (P less than 0.05). Intravenous infusion of L-NAME also blocked the inhibitory effect of vagal and antral stimulation but left the tetrodotoxin-insensitive action of intra-arterial vasoactive intestinal peptide (VIP) and sodium nitroprusside unchanged. L-Arginine reversed the effect of L-NAME whereas D-arginine did not. L-NAME enhanced pyloric contractions to intra-arterial acetylcholine. The NANC inhibition of the substance P-stimulated pyloric response in vitro was blocked by L-NAME and reversed by addition of L-arginine. Sodium nitroprusside was effective as a relaxant in vitro but VIP was not. These data suggest that metabolites of L-arginine mediate neural inhibition of canine pyloric motor activity.

Animals↗

Renal medullary interstitial infusion of diltiazem alters sodium and water excretion in rats.

The role of renal papillary blood flow in regulation of fluid and electrolyte excretion was examined. The effects of an acute infusion of diltiazem (5 micrograms.kg-1 x min-1) into the renal medullary interstitium on papillary blood flow and sodium and water excretion were studied. Changes of renal blood flow were measured using an electromagnetic flow probe. Cortical and papillary blood flows were measured using laser-Doppler flowmetry. Renal and cortical blood flows were unchanged during medullary interstitial infusion of diltiazem, but papillary blood flow increased 26% (P < 0.05) and remained elevated for 1 h after diltiazem infusion was discontinued. Glomerular filtration rate (GFR) of the infused kidney increased by 21% from a control of 1.0 +/- 0.1 ml.min-1 x g-1 during infusion of diltiazem (P < 0.05), but it returned to control after diltiazem infusion was stopped. Urine flow and sodium excretion increased by 70% (P < 0.05), and fractional sodium excretion rose from 1.5 +/- 0.2 to 2.4 +/- 0.3% of the filtered load during the hour after diltiazem infusion. Renal blood flow, cortical and papillary blood flow, GFR, urine flow, and sodium excretion in the 0.9% sodium chloride vehicle-infused kidney were not significantly altered during the experiment. Intravenous infusion of the same dose of diltiazem (5 micrograms.kg-1 x min-1) increased GFR by 22%, but had no effect on urine flow and sodium excretion. These results indicate that renal medullary interstitial infusion of diltiazem selectively increased renal papillary blood flow, which was associated with an increase of sodium and water excretion.

Animals↗

Volatile N-nitrosamines in salted fish samples from high- and low-risk areas for NPC in China.

Four carcinogenic volatile nitrosamines (N-dimethylnitrosamine, NDMA; N-diethylnitrosamine, NDEA; N-nitrosopyrroline, NPYR; and N-nirosopiperilidine, NPIP) were screened in twenty specimens of salted fish collected from areas in China with different nasopharyngeal carcinoma (NPC) mortality rates. The highest NDMA, NDEA and total N-nitrosamine contents (322.92, 50.27 and 373.19 micrograms/kg, respectively) were found in the samples from Sihui, one of the areas with highest NPC mortality. The lowest contents (12.64, 7.65 and 20.29 micrograms/kg, respectively) were seen in the samples from Shanghai, the area with the lowest mortality from NPC in the study. These results confirm that there are appreciable levels of nitrosamines in the salted fishes consumed by residents in high-risk areas of NPC in China.

Animals↗

[ELISA of serum isoferritin and its clinical application].

Serum isoferritin levels were detected by ELISA in 96 normal, 11 cases of hepatocellular carcinoma (HCC), 28 breast cancer (BC), 31 lung cancer (LC), 26 breast fibroma, 11 pneumonia and 11 tuberculosis. The results reveal significant differences of serum isoferritin levels between the normals and the patients, and between the malignant cases and benign cases (P < 0.01). Serum isoferritin demonstrates higher sensitivity in detecting HCC, LC and BC and thus is of great value in the differential diagnosis of these cancers.

Adult↗

[Effects of Cordyceps sinensis (CS) on in vitro natural killer cells].

The effect of Cordyceps sinensis (CS) on peripheral NK cells from healthy persons and leukemia patients were studied. The results showed that CS could argument the NK cell activity, meanwhile, the dose-dependent effect was found within the range of dosage adopted (r = 0.984, P less than 0.01; r = 0.988, P less than 0.01). Furthermore, CS could also improve the CD16 marker expression on lymphocytes and the binding capacity to K562 cells. Cytotoxicity could not present when the PBNCs were co-incubated with CS. These results suggested that CS could be exploited and utilized as an approach of biological responsive modifier therapy (BRMT) in the treatment of leukemia.

Antigens, CD↗

[Clinical significance on expression of the ras gene product P21 in human cervical carcinoma tissues].

Using MAB-P21 as a probe, the expression of gene product was studied by immunohistochemical ABC method, ABC staining of gel electrophoresis and ELISA quantitative analysis. The expression of P21 was detected in 107 cases of uterine cervix tissues, among which 70 were cervical carcinoma, 30 were chronic cervicitis and 7 normal cervix. Experimental results showed that obviously positive expression was noted in the specimens of cervical carcinoma and its positive rate was 72.8% (51/70). It was observed that the expression of P21 varied with grades of cell differentiation in cervical carcinoma. The level of P21 expression in high differentiated type was higher than that of the middle and low differentiated types. On the contrary, there was no detectable ras P21 in the normal cervix tissue and only 2 cases of cervicitis expressed positively (2/30). The results of ABC staining of electrophoresis showed that there was a P21 special staining band in cervical carcinoma tissues. And the contents of P21 protein were higher in cervical carcinoma than in normal cervix and cervicitis (t test, P less than 0.001). The expression of P21 was considerably enhanced in malignant tissue as compared with that in benign lesion.

Adenocarcinoma↗

Cardiovascular effects of thyrotropin-releasing hormone in normotensive and hypotensive rats: role of rostral ventrolateral medulla.

To ascertain the central mechanism of the effects of thyrotropin-releasing hormone (TRH) on the cardiovascular system, we evaluated the effects of this neuropeptide on unit fires in the rostral ventro-lateral medulla (RVL), mean arterial pressure (MAP), and heart rate (HR) in normotensive and hypotensive rats. Intracerebroventricular injection (i.c.v.) of 10 micrograms TRH significantly increased MAP and HR in both normotensive and hypotensive rats. No similar effects were observed after saline injection. If electrolytic lesions of bilateral RVL were made, the cardiovascular effects of TRH i.c.v. failed to occur. TRH i.c.v. markedly increased the firing frequency of most units in the RVL. In particular, TRH i.c.v. increased the firing frequency of most units excitatory to a fall in MAP and decreased the firing frequency of most units inhibitory to a fall in MAP in normotensive rats. Moreover, a drop of MAP as low as 40 mmHg for 10 min resulted in an increase of the firing frequency of most units. The effect of TRH i.c.v. on the RVL units in the hypotensive rats was similar to that in the normotensive rats. Our findings suggest that TRH is able to intensify the cardiovascular activities and the RVL plays a key role in the effects of TRH on the cardiovascular system in both normotensive and hypotensive rats.

Animals↗

A study on optimum load for physical work.

Five healthy men were chosen as experimental subjects and were divided into groups at random. The subjects walked with a load in a shoulder-waist-back manner on the treadmill at the speed of 5, 7 and 9 km h-1. The parameters measured were as follows: oxygen expenditure, energy consumption, heart rate and self appraisal. Based on the experimental results and analysis of multiple regression, the authors suggested that physical loading should not exceed 25 kg (i.e. roughly equal to 39% of average body weight of male Chinese), when the walking speed was at 5 km h-1. The suitable loading at physical work would be 20 kg (i.e. equal to 31% of the average body weight of male Chinese).

Adult↗

[Study on the relationship between congenital toxoplasmosis and monsters of cleft lip and palate accompanied by multiple malformation]

Toxoplasomsis is a zoonotic disease resulted from toxoplasma infection,This paper reports ten monsters that suffered from congenital cleft lip and palate accompanied antigens(RCEP,COA test) were positive.Toxoplasma antibodies (IHA,IFA,RIPEGA test) in mothers' serum were also positive.Microscopic examination revealed toxoplasma trophozoites and pseudocysts in the tissue of cleft lip and palate as well as viscera.In addition,We used SPA method to reveal toxoplasma in the tissue.We indicate that toxoplasma infection of pregnant women is one of the cause of monsters.It is the important biological factor and closely related to eugenics.Stomatologists must pay attention to this etiology.

Journal Article↗

Comparative in vitro studies of the potentiation of tumor necrosis factor (TNF)-alpha, TNF-beta, and TNF-SAM2 cytotoxicity by hyperthermia.

Hyperthermia can strikingly enhance tumor necrosis factor-alpha (TNF-alpha) cytotoxicity in vitro and in vivo. Other forms of TNF may have tumor therapeutic applications and their interaction with hyperthermia should also be assessed. We have compared the effect of heat on the in vitro cytotoxic response of murine L929 and EMT-6 and human T24 tumor cells to three TNF forms; recombinant human TNF-alpha, TNF-beta (lymphotoxin), and TNF-SAM2. A neutral red assay was used to measure toxicity at 18-20 h after initiating the heat treatment. TNF treatment preceded heating by 0-4 h or followed it by 2 h. Heating was done at 39 or 40.5 degrees C for 24 h, 40.5 or 42 degrees C for 1 h, or 43 degrees C for 1-1.5 h. We found that both TNF-beta and TNF-SAM2 toxicities, like that of TNF-alpha, were markedly enhanced by hyperthermia. Neither EMT-6 nor T24 cells responded consistently to any of these TNFs at heat doses up to 1 h at 43 degrees C, but an increment of only 15 min more at 43 degrees C sensitized EMT-6 cells and 1.5 h at 43 degrees C resulted in extensive EMT-6 cell killing. The T24 cells remained resistant except for variable responses at the highest TNF and heat doses. If TNF treatment was begun immediately before or 2 h after beginning to heat the EMT-6 cells, sensitization was reduced or eliminated, respectively, for all three TNF forms relative to protocols in which TNF was added 1, 2, or 4 h before heating.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Number and placement of hydrophobic residues in a longitudinal strip governs helix formation of peptides in the presence of lipid vesicles.

alpha-Helix formation of a peptidyl sequence is stabilized by hydrophobic residues recurring at positions which create a longitudinal hydrophobic strip upon folding of the sequence as a helix against a hydrophobic surface. To test that hypothesis, we measured by circular dichroism the helical coiling on lipid vesicles of nine analogs of a prototypic helix peptide PH-1.0, Leu-Tyr-Gln-Glu-Leu-Gln-Lys-Leu-Thr-Gln-Thr-Leu-Lys. In these analogs, Thr was substituted for 1 or 2 Leu residues in the longitudinal hydrophobic strip Leu1...Leu5..Leu8...Leu12 which forms in the alpha-helical configuration. We found that coiling of analogs of Leu-Tyr-Gln-Glu-Leu-Gln-Lys-Leu-Tyr-Gln-Thr-Leu-Lys on lipid vesicles depends upon the strength and structure of its longitudinal hydrophobic strip.

Amino Acid Sequence↗

Cathepsin B cleavage of Ii from class II MHC alpha- and beta-chains.

Class II MHC-associated invariant chain (Ii) might regulate binding of digested peptides to the Ag binding site (desetope) of class II MHC proteins by directly or allosterically blocking that site until cleavage and release of Ii from MHC alpha- and beta-chains at the time of peptide charging. We examined the cleavage and release of Ii from class II MHC alpha/beta Ii trimers by cathepsin B, which has been shown by others to colocalize with class II MHC molecules in intracellular compartments and to generate antigenic peptide fragments. Cathepsin B at pH 5.0 cleaved and released Ii from class II MHC alpha- and beta-chains. Cathepsin B digested Ii from alpha- and beta-chains in a dose-dependent fashion, yielding 23-, 21-, and 10-kDa fragments. Blockage of cathepsin B activity with leupeptin restored the 2D(nonequilibrium pH gradient gel electrophoresis/SDS) PAGE patterns of Ii and sialic acid-derivatized forms of Ii seen without the protease. The fragmentation pattern of cathepsin D treatment was different from that of cathepsin B, yielding 25-kDa intermediates.

Antigens, Differentiation, B-Lymphocyte↗

Prediction of alpha helices and T cell-presented sequences in proteins with algorithms based on strip-of-helix hydrophobicity index.

Recurrent aliphatic hydrophobic amino acids which occur in the sequence of a protein or a peptide at positions which form an axial, hydrophobic strip when the sequence is coiled as an alpha helix might stabilize coiling against hydrophobic surfaces. That effect can lead to helix formation against hydrophobic cores of nascent proteins or excised T cell-presented peptides and to protease protection and scavenging for presentation by MHC molecules. Such consensus sequences of recurrent hydrophobicity creating a scavenger "S" site might overlap to varying degrees the T cell-presented "T" epitope which actually sits in the antigen-binding site of a MHC molecules, as long as a cleavage "C" site does not fall between them when they are relatively separated. Cooperatively among the residues in an axial, hydrophobic strip to stabilize helix formation is reflected in the SOHHI, which is the mean hydrophobicity of residues in such potential strips. Algorithms based on the SOHHI, with additional considerations related to length and caps, lead to sensitive and efficient predictions of structural helices and of T cell-presented epitopes. In experimental tests of these ideas, the SOHHI was found to correlate to helical coiling of amphiphilic peptides in the presence of lipid vesicles. These principles lead to hypotheses to alter the potency and range of MHC restriction of peptide vaccines or to decrease the immunogenicity of therapeutic proteins.

Algorithms↗

Common principles in protein folding and antigen presentation.

The regular recurrence of hydrophobic amino acid residues along a peptide sequence determines the formation of a longitudinal hydrophobic strip when the peptide forms an alpha-helix. An understanding of the ways this may affect both folding of nascent proteins and antigen presentation should facilitate vaccine and therapeutics design.

Amino Acid Sequence↗