Search PubMed⌕ Search

Biomedical subjects

L Shen

Publications and source records attributed to L Shen.

At least 253 records · Page 14Linked to original sources

Verapamil regulation of a defective SR release channel in the cardiomyopathic Syrian hamster.

The Bio 14.6 Cardiomyopathic Syrian Hamster (CMH) has an autosomal recessive disease characterized by intracellular calcium overload, cardiac and skeletal myopathies and premature death from congestive heart failure. Early treatment of these animals with the calcium antagonist, verapamil (V), prevents the development of the disease. We have previously provided evidence supporting a specific defect in the ryanodine-sensitive SR calcium release channel (SRCRC) in CMH. We now provide physiologic and biochemical evidence that V modulates SRCRC. Papillary muscles prepared from F1B control hamsters (F1B) revealed an enhanced inotropic responsiveness to V and ryanodine (R) with age, not seen with CMH. CMH papillary muscles demonstrated paradoxical positive inotropic effects of V and R not shared with F1B. The positive inotropic effects of V and R were not additive. V enhanced the affinity (decreased KD) of [3H]ryanodine binding to cardiac membranes. Thus, V may prevent the overt manifestations of genetic disease in CMH by modulating a defective ryanodine-sensitive SR release channel.

Animals↗

Immunization with lentivirus-like particles elicits a potent SIV-specific recall cytotoxic T-lymphocyte response in rhesus monkeys.

An effective acquired immunodeficiency syndrome (AIDS) vaccine should be capable of eliciting human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte (CTL) responses. We have explored the use of lentivirus-like particles produced in mammalian cells infected with a recombinant vaccinia virus to immunize for the induction of CTL in the simian immunodeficiency virus (SIV)/rhesus monkey model for AIDS. SIV-like particles in a threonyl-MDP-based adjuvant did not elicit a high frequency of SIV gag-specific effector cells in naive rhesus monkeys. However, immunization with these particles elicited a potent recall CTL response in monkeys previously vaccinated with a recombinant vaccinia-SIV virus. These observations suggest that poxvirus-produced virus-like particles may represent a safe immunogen for use in periodic boosting to maintain viable cell-mediated immunity to the AIDS virus.

Animals↗

Positive inotropic effect of acetylcysteine in cardiomyopathic Syrian hamsters.

Several laboratories have provided indirect evidence that the myocardium of the cardiomyopathic Syrian hamster (CMH) is chronically ischemic on the basis of microvascular spasm. We previously reported evidence supporting a defect in the ryanodine-sensitive sarcoplasmic reticulum calcium release channel (SRCRC) in CMH. A relation between alterations in SRCRC and chronic ischemia has not yet been explored. A potential mechanism could be the effects of changes in redox state on thiol groups. Thiol reagents have previously been shown to regulate calcium release from SRCRC. Accordingly, we studied the inotropic effects of the sulfhydryl donors, acetylcysteine (AC), cysteine, and cystine in CMH. AC was a positive inotrope in isolated papillary muscles prepared from CMH, but not F1B controls (F1B) (p < 0.01). No significant differences were noted in inotropic responses to cysteine or cystine. AC blunted the response of CMH > F1B control papillary muscle preparations to stimulation frequency (p < 0.01). The actual tension generated (in mg/mm2) by CMH was no longer different than F1B with addition of AC (10(-3) M), ryanodine (10(-8) M), or verapamil (5 x 10(-7) M). These findings are consistent with a defect in SRCRC in CMH. This defect may be primary or may provide a novel mechanism for hibernating myocardium owing to chronic ischemia.

Acetylcysteine↗

The octamer/mu E4 region of the immunoglobulin heavy-chain enhancer mediates gene repression in myeloma x T-lymphoma hybrids.

We have shown previously that the immunoglobulin heavy-chain enhancer acts as a repressor of gene transcription in hybrids between immunoglobulin-producing myelomas and a T-lymphoma line. We have now mapped this repressive activity to a 51-bp enhancer subfragment which contains the octamer and mu E4 protein-binding motifs. Even a single copy of this subfragment will repress gene expression in hybrid cells. Mutational analyses of the repressor fragment suggest that in non-B cells, a strong transcriptional repressor(s) functions through the same motifs important for gene activation in B cells. Changes in chromatin structure that accompany reporter gene repression suggest a general mechanism for prohibiting immunoglobulin heavy-chain locus activation in inappropriate cell types.

Animals↗

Plasmid analysis and phage typing in the study of staphylococcal colonization and disease in newborn infants.

Plasmid analysis, bacteriophage typing and antibiograms were used to detect the source and rate of Staphylococcus aureus colonization and disease in newborn infants in a nursery. Staphylococcal colonization on the nasal mucosa and umbilicus of 140 neonates took place within 12 hours after birth. The colonization rates reached 100% from the fourth day onward and fell to 66.7%, 25.5% and 17.5% by the age of 1 month, 6 months and 1 year, respectively. The incidence of nursery-acquired infection caused by S. aureus was at least 16.4%. All infections were confined to the skin or mucosa and were not serious. It is believed that the S. aureus which colonized and infected the newborn infants mainly originated from the nares and the hands of nurses, because only S. aureus strains from nurses and infected infants had the same phage patterns (52/52A/47/53/75/77/81) and carried 2 plasmids of the same size (1.4 and 1.7 Md), whereas S. aureus isolated from other sources did not have the same phage patterns or plasmid profiles. In view of the results of this study, it is considered that the importance of careful washing of the hands of personnel before and after handling infants should be emphasized.

Bacteriophage Typing↗

[Neuroendocrine markers in lung cancer].

UNLABELLED: 80 cases of resected lung cancer were studied using five different neuroendocrine (NE) markers with the avidin-biotin-peroxidase complex method. RESULTS: (1) The positive rates of carcinoid and small cell lung cancer (SCLC) expressing NE markers was 100% and 93.8% respectively, and the positive rate of non-SCLC (except carcinoid) was 24.1% (2) If NE granules were found by electron microscope, NE markers all gave positive reaction. (3) The positive sections on argyrophil stain all expressed NE markers. (4) Positive NE markers for tumors > 5 cm was 64.1%, but in non-SCLC, only 31.8% of tumors larger than 5 cm diameter had negative NE. The above results indicate that the use of NE markers in lung cancer is reliable, sensitive and practical. The relation between NE differentiation and biological behavior requires further study.

Biomarkers, Tumor↗

[Analysis of tramadol and its metabolites in human urine].

A GC-MS method for the analysis of tramadol and its four metabolites in human urine is described. The urine samples were acid hydrolyzed with hydrochloric acid, cleaned with diethyl ether and extracted with dichloromethane-isopropanol (9:1). After derivatization, the solution was analyzed with GC-MSD. Tramadol and its 4 metabolites were detected in urine samples 2-40 hours after oral administration. The recovery of tramadol was 85.2% +/- 5.4 (n = 3), the detection limit was down to 12.5 pg. The derivatization methods was discussed.

Gas Chromatography-Mass Spectrometry↗

[Analysis of dextromethorphan and its metabolites in human urine by using gas chromatography-mass spectrometry].

A GC-MS method for the analysis of dextromethorphan and its metabolites is described. The urine sample was hydrolyzed with HCl, extracted with diethyl ether and derivatized with MSTFA (N-methyl-N-trimethylsilyltrifluoroacetamide)-MBTFA (N-methyl-bistrifluoroacetamide). Dextromethorphan and its 3 metabolites were detected in urine samples within 2-60 h after administration of the drug. Their structures and the variation of their concentration in urine were determined. The detection limit of dextromethorphan is 10 ng.

Dextromethorphan↗

[Effects of combined therapy of traditional Chinese and Western medicine on C-reactive protein in post-debridement patients].

Closely monitoring whether the secondary infection in the patients of post-debridement occurred or not and appropriately treating these patients were the important ways to reduce the incidence of infection. Through estimating the level of the serum C-reactive protein (CRP) as the monitoring index of infection, dynamically observed the effect of the combined traditional Chinese and Western medicine therapy (TCM-WM) on CRP after debridement, as was compared with the effect of the Western medicine therapy (WM) group in which only the WM was administrated. The result showed that the levels of CRP decreased in both TCM-WM and WM group on 4th day after the operation, but the level of CRP in former group was lower than that in latter one, the difference was very significant (P < 0.001). So that, it was assumed that TCM-WM significantly excelled the WM on affecting the level of CRP and reducing the incidence of infection. It was suggested that CRP could be used as an effective and objective index to determine whether the secondary infection has happened and to assess the efficacy of some drugs.

Adolescent↗

Cytotoxic T lymphocytes do not appear to select for mutations in an immunodominant epitope of simian immunodeficiency virus gag.

Studies to date assessing HIV escape from CTL in vivo have yielded conflicting results. Previous studies have demonstrated that simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys expressing the MHC class I allele Mamu-A*01 reproducibly develop a gag-specific CTL response limited to a 9-amino acid epitope of the SIVmac gag protein (residues 182-190 within peptide 11C). To determine whether CTL have a role in selecting for AIDS virus mutants, we examined mutations in SIVmac proviral DNA encoding this gag CTL epitope in PBL of infected rhesus monkeys. Three Mamu-A*01+ rhesus monkeys were infected with SIVmac and assessed for gag- and peptide 11C-specific CTL responses. This specific CTL response was maintained in two monkeys, but lost in the third animal 2 yr after infection. The generation of proviral gag mutations was then determined by sequencing 500-bp proviral fragments amplified from fresh PBL obtained from the monkeys more than 2.5 yr after infection. Although numerous point mutations were characterized in 131 polymerase chain reaction-generated clones of SIVmac gag, only four mutations within the gag CTL epitope-coding region of the genome were identified. Comparison of synonymous and nonsynonymous nucleotide substitutions in the regions encoding peptide 11C (p11C) and the flanking gag protein indicated a lack of selective pressure for viral mutations in the CTL epitope coding region. Interestingly, a predominant gag mutant encoding a single amino acid change in p11C was found in a monkey which lost its CTL activity. However, even in this setting there was no evidence for selection of mutations in the CTL epitope coding region when compared with the flanking region. Furthermore, synthetic peptides corresponding to all naturally occurring variants in the gag epitope-coding region were recognized by cloned and bulk cultured effector cells of the infected monkeys with persistent CTL. These results indicate that SIVmac gag- and p11C-specific CTL do not select for mutations in the immunodominant epitope-coding region and that the naturally occurring mutants do not appear to escape CTL recognition.

Amino Acid Sequence↗

Vaccination of rhesus monkeys with synthetic peptide in a fusogenic proteoliposome elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes.

An effective vaccine against the human immunodeficiency virus should be capable of eliciting both an antibody and a cytotoxic T lymphocyte (CTL) response. However, when viral proteins and peptides are formulated with traditional immunological adjuvants and inoculated via a route acceptable for use in humans, they have not been successful at eliciting virus-specific, major histocompatibility complex (MHC) class I-restricted CTL. We have designed a novel viral subunit vaccine by encapsulating a previously defined synthetic peptide CTL epitope of the simian immunodeficiency virus (SIV) gag protein within a proteoliposome capable of attaching to and fusing with plasma membranes. Upon fusing, the encapsulated contents of this proteoliposome can enter the MHC class I processing pathway through the cytoplasm. In this report, we show that after a single intramuscular vaccination, rhesus monkeys develop a CD8+ cell-mediated, MHC class I-restricted CTL response that recognizes the synthetic peptide immunogen. The induced CTL also demonstrate antiviral immunity by recognizing SIV gag protein endogenously processed by target cells infected with SIV/vaccinia recombinant virus. These results demonstrate that virus-specific, MHC class I-restricted, CD8+ CTL can be elicited by a safe, nonreplicating viral subunit vaccine in a primate model for acquired immune deficiency syndrome. Moreover, the proteoliposome vaccine formation described can include multiple synthetic peptide epitopes, and, thus, offers a simple means of generating antiviral cell-mediated immunity in a genetically heterogeneous population.

Amino Acid Sequence↗

A monoclonal antibody specific for immunoglobulin A receptor triggers polymorphonuclear neutrophil superoxide release.

An immunoglobulin M (IgM) monoclonal antibody, My43, specific for IgA Fc receptor (Fc alpha R) on human monocytes, bound to human polymorphonuclear neutrophils (PMNs) and inhibited their ability to bind IgA but not IgG. It was observed that the PMN oxidative burst was induced by both polymeric IgA and aggregated IgG, whereas IgM was without effect. The IgG-mediated oxidative burst was inhibited by anti-Fc gamma RII Fab and anti-Fc gamma RIII F(ab')2 but not by My43. Conversely, the IgA-mediated oxidative burst was inhibited by My43 but not by anti-Fc gamma RII or anti-Fc gamma RIII. When anti-Fc receptor monoclonal antibodies (mAbs) were used directly as ligands, it was observed that both anti-Fc gamma RII Fab and anti-Fc gamma RII F(ab')2 promoted the oxidative burst when cross-linked. Moreover, My43, when cross-linked with F(ab')2 antimouse IgM, also triggered the oxidative burst, whereas an IgM anti-CD15 mAb, PM81, did not stimulate function. This demonstrates that IgA receptors on PMNs are function-triggering molecules and that an anti-IgA receptor mAb may be substituted as a ligand.

Antibodies, Monoclonal↗

Selenium content of goat milk and its distribution in protein fractions.

This study reports on selenium distribution in goat milk. Skim milk was found to contain the major part (94%) of total milk selenium. The selenium distribution over casein and whey protein fractions depends on the separation method used, but irrespective of these methods, skim milk selenium is mainly associated with the casein fraction (greater than 69%). Approximately 9%, 7% and 24% of selenium is removed by dialysis (molecular cutoff 10-12 kDa) from skim milk, casein and whey respectively, indicating a major association of selenium with milk proteins. This observation is confirmed by selenium analysis of individual caseins and whey proteins isolated through ion-exchange chromatography and gel filtration. Selenium concentrations of the different isolated milk proteins show considerable variation (caseins: 294-550 ng Se/g; whey proteins: 217-457 ng Se/g).

Animals↗

Receptors for IgA on phagocytic cells.

IgA receptors have been detected on monocytes, polymorphonuclear neutrophils (PMNs) and eosinophils, and on phagocytic cells at mucosal sites. These receptors bind both secretory and serum forms of immunoglobulin A (IgA) and require the Ca2 region of the IgA molecule for ligand recognition. Monocytes and PMNs modulate their expression of the IgA receptor upon treatment with cytokines, such as granulocyto-macrophage colony-stimulating factor, and lipopolysaccharide. Purified IgA receptors appear as heavily glycosylated molecules with an average molecular weight of 60 kD, dropping to 32 and 36 kD upon treatment with N-glycanase. The cDNA sequence encoding the IgA receptor has been determined by expression cloning, and predicts that the receptor consists of two Ig-like extracellular domaines, a transmembrane region and a cytoplasmic tail of 41 residues. Ligation of IgA receptors on phagocytic cells by multivalent IgA complexes induces a variety of responses, including superoxide generation, release of inflammatory mediators, phagocytosis, and killing of various pathogenic microorganisms. Thus the apparent role of these receptors is to amplify the protective effects of the IgA antibody, a function of potential importance to mucosal defense.

Animals↗

Radioligand binding and inotropic effects of ryanodine in the cardiomyopathic Syrian hamster.

We compared the radioligand-binding and inotropic effects of ryanodine [known specific regulator of sarcoplasmic reticulum (SR) calcium release channel] on BIO 14.6 cardiomyopathic Syrian hamsters with those on age-matched F1B controls. Scatchard analyses of [3H]ryanodine binding to cardiac membranes prepared from 1-2-month-old BIO 14.6 and F1B Syrian hamsters revealed the presence of a significant increase in binding capacity (Bmax = 942 +/- 49 vs. 567 +/- 33 fmol/mg protein) with no difference in affinity (KD = 3.9 +/- 0.4 vs. 3.5 +/- 0.5 nM, p less than 0.01). Ryanodine is a significantly less potent negative inotrope in isolated papillary muscles prepared from 1-2-month-old BIO 14.6 hamsters than in muscles from F1B controls (IC50 = 4.3 +/- 1 vs. 0.5 +/- 0.4 microM, p less than 0.05). Ryanodine was 200-fold less potent in the 4-6-month-old myopathic muscles than in controls (IC50 = 20 +/- 5 vs. 0.1 +/- 0.01 microM, p less than 0.01). A paradoxic positive inotropic effect of ryanodine observed in 4-6-month-old myopathic muscles at low concentrations was not seen in controls (ECmax = 126 +/- 5% at 1 +/- 0.1 x 10(-8) M). These data support the presence of a defect both biochemical and physiologic in the ryanodine-sensitive SR calcium release channel in the BIO 14.6 cardiomyopathic Syrian hamster. Purification, cloning, sequencing, and expression studies will be required to distinguish among primary, secondary, intrinsic, and regulatory defects in the ryanodine-sensitive SR calcium release channel in the cardiomyopathic Syrian hamster.

Animals↗

[Effects of fertilization on yield of Asparagus cochinchinensis (Lour.) Merr].

The experiment revealed that the use of various kinds of fertilizers has apparent effect on the yield of Asparagus cochinchinensis during its growth period. Nitrogen fertilizer and compound fertilizer are suitable for the seeding period, while compound fertilizer, phosphorus and potassium fertilizers are suitable for the period of root forming. The quantity of fertilizer to be used depends on the growing and soil conditions.

Fertilizers↗

[Analysis of genetic models and gene effects on main agronomy characters in rapeseed].

According to four different genetic models, the genetic patterns of 8 agronomy traits were analysed by using the data of 24 generations which included positive and negative cross of 81008 x Tower, both of the varieties are of good quality. The results showed that none of 8 characters could fit in with additive-dominance models. Epistasis was found in all of these characters, and it has significant effect on generation means. Seed weight/plant and some other main yield characters are controlled by duplicate interaction genes. The interaction between triple genes or multiple genes needs to be utilized in yield heterosis.

Brassica↗