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Biomedical subjects

J Shi

Publications and source records attributed to J Shi.

At least 307 records · Page 17Linked to original sources

Secretion of recombinant human IgE-Fc by mammalian cells and biological activity of glycosylation site mutants.

We have constructed an expression vector that leads to secretion of the whole Fc of human immunoglobulin E (hIgE-Fc) from mammalian cells at levels up to 100 mg/l of culture. Two surface glycosylation sites at Asn265 and Asn371 have been changed to glutamine, to obtain a more homogeneous preparation of hIgE-Fc for structural studies. Comparison of wild-type and mutant products revealed that Asn371 is rarely glycosylated in Chinese hamster ovary cells. Both the double mutant and wild-type hIgE-Fc bind to the high-affinity IgE receptor, Fc epsilon RI, with about the same affinity as myeloma IgE (Ka in the range 10(10)-10(11) M-1), and were able to sensitize isolated human basophils for anti-IgE triggering of histamine release. However, only the double mutant hIgE-Fc approached the affinity of myeloma IgE for the low-affinity receptor, Fc epsilon RII (Ka = 7.3 x 10(7) M-1), whereas the wild-type hIgE-Fc bound with a 10-fold lower affinity (Ka = 4.1 x 10(6) M-1).

Amino Acid Sequence↗

Kinetics and dynamics of sematilide.

Sematilide HCl is a novel class III antiarrhythmic drug. The goals of this study in volunteers were to determine the pharmacokinetics, effect (QTc interval), and tolerability after intravenous and oral administration of 25 mg of the drug. Plasma and urine concentrations were measured by a specific high-performance liquid chromatography method. Pharmacokinetic data analysis used a compartment model independent approach. An effect on QTc was observed only after intravenous administration, and its relationship to the plasma concentration showed a counterclockwise hysteresis. A semiparametric approach was used to collapse the hysteresis and then evaluate the effect-site-concentration-to-effect relationship. After intravenous and oral administration, 75.1 (6.5)% (mean +/- SD) and 36.0 (11.5)% of the dose was excreted unchanged in urine, respectively. The respective renal clearances were 250 (41) ml.min-1 and 222 (44) ml.min-1. The bioavailability of sematilide was 0.47 (0.15). A maximum percent effect on QTc of 12 (1)% occurred with a delay of 14 min after termination of an intravenous infusion of 10 min. After collapsing the hysteresis, the pharmacokinetic-pharmacodynamic data could be fitted appropriately by a linear model in four subjects and by an Emax model in two subjects. Sematilide HCl was well tolerated.

Administration, Oral↗

Influence of dietary beta-glucan on growth performance, nonspecific immunity, and resistance to Streptococcus suis infection in weanling pigs.

Three experiments, using 344 pigs, were conducted to evaluate the influence of beta-glucan on growth performance, neutrophil and macrophage function, haptoglobin production, and resistance to Streptococcus suis challenge in weanling pigs. In Exp. 1, 144 pigs were used to evaluate the influence of .1% dietary beta-glucan in a soybean meal- or milk protein-based diet on growth performance and neutrophil function. Pigs fed beta-glucan from d 7 to 14 after weaning had lower ADFI (P < .01) and, although not significant, ADG was lower for pigs fed beta-glucan than for pigs fed control diets. However, no differences were observed in growth performance or neutrophil function for pigs fed control or diets containing beta-glucan from d 7 to 35 after weaning. Experiment 2 was a 28-d growth assay in which pigs were fed a diet with or without .1% beta-glucan, containing 7.5% spray-dried plasma protein and 25% dried whey from d 0 to 14 after weaning. Pigs then were fed corn-soybean mealbased diets containing 2.5% spray-dried blood meal and 10% dried whey. No differences in growth performance were observed. Experiment 3 was a 35-d assay to evaluate growth performance, neutrophil and macrophage function, and plasma haptoglobin concentration. Pigs were challenged on d 28 postweaning with intravenous S. suis. In Exp. 3, pigs were fed diets without or with .025 or .05% beta-glucan. Dietary beta-glucan did not influence neutrophil or macrophage function. However, pigs fed diets containing .025% beta-glucan had increased (P < .05) ADG and ADFI and were heavier (P < .05) on d 28 after weaning than pigs fed the control diet. No differences in feed efficiency (G/F) were detected between treatments. Pigs fed beta-glucan had decreased (P < .10) plasma haptoglobin on d 14, 21, and 28 after weaning. However, Fisher's Exact test revealed that more (P < .04) pigs fed a diet containing .025% beta-glucan died by d 12 after challenge with S. suis. In conclusion, these data suggest the existence of a complex interaction involving growth performance and resistance to S. suis in pigs fed .025% beta-glucan.

Aging↗

Testing a model of aging in animal experiments.

A stochastic model of aging is developed in terms of accumulation and expression of intracellular lesions caused by environment or intrinsic genetic program. In contrast to the commonly used Gompertz-Makeham approach to the parametric analysis of mortality data, the model yields a hazard function that is bounded from above. For testing the model in experiments aimed at studying animal longevity, a Kolmogorov-type statistical test is presented with regard to the hypothesis involving unknown parameters. Examples concerning longevity of intact animals of two different species, as well as the effect of a prolonged irradiation at a low dose rate, are given to illustrate the model application and goodness-of-fit testing. The results of the analysis of published data show that the rate of lesion formation is not sustained at a constant level throughout life, though in some cases its variations with age can be considered negligible.

Aging↗

[Relationship between bone fluoride content, pathological change in bone of aborted fetuses and maternal fluoride level].

Relationship between bone fluoride content, pathological change in bone of aborted fetuses and maternal fluoride level was studied in 46 pregnant women and their inducedly-aborted fetuses. Results showed fluoride content in fetal femur averaged 368.2 micrograms/g, and 41.4% of the bone with pathological change. Fluoride levels in maternal urine and amniotic fluid and fluoride content in fetal femur and pathological change in fetal femur appeared a positive correlation between them. Femur fluoride content and pathological change of bone in fetuses born to mothers with mottling teeth were significantly greater than to those without them. Pathological change in fetal femur presented dose-response relationship with their bone fluoride content. When the latter reached greater than 500 micrograms/g, pathological changes occurred in 90% of the bone.

Adult↗

[Protein analysis of 6 crude drugs and their processed products by polyacrylamide gel electrophoresis technique].

In this paper, the proteins in 6 crude drugs (Prunus persica; P. armeniaca; Dolichos lablab; Strychnos nux-vomica; Mylabris phalerata; Whitmania pigra) and their processed products were analysed by polyacrylamide gel electrophoresis technique, and the effect of different processing methods on the quantity and kind of protein was explored. Protein electrophorograms of 20 samples are drawn.

Animals↗

[Influences of capsaicin and electroacupuncture at "point" on acetylcholine (ACh) release in the spinal dorsal horn of rats].

The dynamic changes of ACh activity in the spinal dorsal horn of rats were recorded by ACh ion selective microelectrodes. The influence of applying capsaicin to the spinal surface, administering anti-SP surum to the interior of dorsal horn, cutting off dorsal roots and electroacupuncturing at "points" on the ACh activity were studied. The results showed that electroacupuncture at "points" and capsaicin could facilitate ACh release of the spinal dorsal horn, it was fully inhibited by cutting off dorsal roots or obviously inhibited by administering anti-SP surum. The above results indicated that ACh might participate in the primary afferent of painsensation and acupuncture sensation as a neurotransmitter and SP might adjust the release of ACh in spinal dorsal horn.

Acetylcholine↗

[Detection of CgA mRNA in neuroendocrine cells in gastric carcinoma by in situ hybridization].

Fresh gastric carcinoma specimens from 17 cases were collected. The neuroendocrine (NE) cells in gastric carcinoma (GC) and gastric mucosa adjacent to the carcinoma (GMAC) were observed using in situ hybridization of chromogranin A (CgA) oligonucleotide probe and compared with immunohistochemistry of CgA antibody. 5 of the 17 cases of GC showed CgA mRNA positive expression and 7 of the 17 cases expressed CgA protein positively. The simultaneous expression of mRNA and protein of CgA was present in 4 cases. The NE cells in GC not only can store and secrete CgA protein products but also possess the ability to synthesize NE products from gene expression.

APUD Cells↗

[Collateral projections of gamma-aminobutyric acid positive neurons from the lateral superior nucleus to the cochlea and cochlear nucleus in guinea pigs].

Collateral projections of gamma-aminobutyric acid (GABA) neurons from the lateral superior olivary nucleus (LSO) to the cochlea and cochlear nuclei in the guinea pigs were studied by injection of two retrograde fluorescent neuronal tracers. For experiments, fast blue (FB) was injected into the scala tympani of one cochlea and diamidine yellow (DY) was injected into cochlear nuclei of the same side. The results showed that the FB-labelled cells and DY-labelled cells constituted approximately 80.8% and 12.4%, respectively; FB and DY double-labelled cells constituted about 6%; FB and DY labelled cells with GABA constituted about 0.7% in the ipsilateral LSO. In the contralateral LSO, the FB and DY labelled cells were less than those of ipsilateral LSO and no FB-DY double-labelled cells could be found. Our results suggest that there are collateral projections of GABA neurons from ipsilateral LSO to the organ of Corti and cochlear nuclei in the guinea pig, even though the numbers are few. The results also show that the efferent projections to the cochlea and cochlear nuclei generally come from two different auditory neuronal nuclei.

Amidines↗

A single 43-bp sopC repeat of plasmid mini-F is sufficient to allow assembly of a functional nucleoprotein partition complex.

Stable maintenance of the low-copy-number mini-F plasmid in Escherichia coli is dependent on a functional partition system. The sop partition region encodes proteins SopA and SopB and a cis-acting element sopC, which contains multiple sites to which SopB binds. We have found that SopB protein acting at sopC in vivo is associated with a marked effect on plasmid DNA supercoiling, which may reflect the formation of a wrapped nucleoprotein complex. In this study, we demonstrate that a functional partition complex can form with a single 43-bp SopB binding site. Our experiments suggest that SopB bound at a single site nucleates the binding of additional SopB protein and wrapping of adjacent DNA sequences, such that approximately equal numbers of supercoils are restrained regardless of the number of tandem sopC repeats present. It is likely that this unusual nucleoprotein complex allows interaction of the plasmid with the partition apparatus.

Base Sequence↗

A study on superoxide dismutase activity of some model compounds.

The synthesis and characteristics of a binuclear ligand N,N,N',N'-tetrakis (2'-benzimidazolyl methyl)-1,4-diethylene amino glycol ether (EGTB) and its series of coordination compounds containing copper(II), iron(III), and manganese(II) with and without exogenous bridging ligand which was imidazolate ion (Im-), bipyridine (bpy), or 1,10-phenanthroline (phen) are reported. Depending on the redox potentials by cyclic voltammetry, the coordination compounds can act as catalysts for the dismutation of superoxide radicals (O2-). The detection of the rate constant of the reaction of superoxide ion with nitroblue tetrazolium (NBT) which is inhibited by superoxide dismutase (SOD) and its model compounds of the EGTB system has been performed by a modified illumination method. The rate constants kQ of the catalytic dismutation have been obtained.

Copper↗

Influence of interleukin-1 on neutrophil function and resistance to Streptococcus suis in neonatal pigs.

Nonspecific immunity is usually lower in neonates than adults. Consequently, enhancing the neonate's nonspecific immune capability may be beneficial for the health and growth performance of young animals. We conducted two experiments in which neonatal pigs were injected with recombinant bovine interleukin-1 beta (rBoIL-1 beta) at 9 to 11 days of age. Three consecutive daily injections of rBoIL-1 beta increased neutrophil and monocyte numbers, which remained elevated until the animals were challenged with Streptococcus suis at 19 days of age. Neutrophil bactericidal activity was greater in interleukin-1-treated pigs than in saline-injected controls. At lower ratios of effector to target cells, neutrophil-mediated, antibody-dependent cellular cytotoxicity was increased in neonates treated with IL-1. However, natural killer cell activity and neutrophil production of superoxide anion were not affected by treatment with IL-1. Expression of CD18 was increased transiently on neutrophils from IL-1-treated pigs at 15 days of age. Severity of the streptococcal infection was less in pigs that were treated with IL-1 at 9 to 11 days of age. These data suggest that IL-1 treatment in neonates may augment nonspecific immune function and disease resistance.

Animals↗

Identification of a proline-arginine-rich antibacterial peptide from neutrophils that is analogous to PR-39, an antibacterial peptide from the small intestine.

Neutrophil nonoxidative defense mechanisms include several low molecular weight antimicrobial peptides. We have isolated a proline-arginine-rich antibacterial peptide from porcine neutrophils. This cationic, low molecular weight peptide has a very high degree of identity (97%) to a bactericidal peptide, PR-39, that has been found in the porcine small intestine. Isolation of the same antimicrobial peptide from both neutrophils and cells of the small intestine in the same species is unique and suggests an important role for this protein in innate immune defenses.

Amino Acid Sequence↗

Comparison of twitch depression of the adductor pollicis and the respiratory muscles. Pharmacodynamic modeling without plasma concentrations.

BACKGROUND: Although the respiratory muscles (the diaphragm and the laryngeal adductors) recover from paralysis more rapidly than does the adductor pollicis, patients can develop complete paralysis of the respiratory muscles, but not of the adductor pollicis, after bolus administration of vecuronium. The authors used a pharmacodynamic model not requiring muscle relaxant plasma concentrations to reconcile these findings. METHODS: The pharmacodynamic model is based on the traditional model, in which: (1) vecuronium concentration at the neuromuscular junction (C(effect)) is a function of the plasma concentration versus time curve and a rate constant for equilibration between plasma and the neuromuscular junction (k(eo)); and (2) effect is a function of C(effect), the steady-state plasma concentration that produces 50% effect (C50), and a factor to explain the sigmoid relationship between concentration and effect. In the absence of vecuronium plasma concentrations, an empiric model (rather than the usual effect compartment model) can be used to mimic the time delay (proportional, but not identical, to 1/k(eo)) between dose and effect. The model can be used to estimate the steady-state infusion rate that produces 50% effect (IR50), equal to the product of C50 and vecuronium plasma clearance; IR50 for different muscle groups then can be compared to assess relative sensitivity. The authors applied this model to published effect data for subjects given 40-70 micrograms/kg vecuronium in whom paralysis of three muscle groups was measured during opioid/propofol anesthesia. RESULTS: For IR50, the ratio of values for the larynx:diaphragm:adductor pollicis was 1.4:1.2:1; for the equilibration constant (inversely proportional to the time delay), the ratio for the respiratory muscles to the adductor pollicis was 2.5:1. CONCLUSIONS: Vecuronium concentrations peak earlier at the respiratory muscles than at the adductor pollicis, possibly the result of greater perfusion to these organs, leading to earlier onset of paralysis. The observation that bolus injection of vecuronium produces greater paralysis of the respiratory muscles than of the adductor pollicis, despite greater resistance of the respiratory muscles, can be explained by differential rates of equilibration between plasma and various muscles.

Humans↗