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S Sun

Publications and source records attributed to S Sun.

At least 163 records · Page 9Linked to original sources
PubMed1998

Reactions of alternate substrates demonstrate stereoelectronic control of reactivity in dialkylglycine decarboxylase.

Kinetic and product analyses of the reactions of dialkylglycine decarboxylase with several alternative substrates are presented. Rate constants for the reactions of amino and keto acids of several substrates decrease logarithmically with increasing side-chain size. Conversely, kcat for L-amino acid decarboxylation increases with side-chain size. These and other data confirm a proposed model for three binding subsites in the active site. In this model, bond making and breaking in both the decarboxylation and transamination half-reactions occurs at the "A" subsite, which maintains the scissile bond aligned with the p orbitals of the conjugated aldimine and thus maximizes stereoelectronic effects. This strongly supports the proposal by Dunathan (Proc. Natl. Acad. Sci. U.S.A. 55, 712-716) that PLP-dependent enzymes can largely control reaction specificity by specific orientation about C alpha in the external aldimine intermediate. The "B" subsite can accept either an alkyl or a carboxylate group, while the "C" subsite accepts only small alkyl groups. This model predicts the existence of nonproductive binding modes for amino acids, which is proposed to be the ultimate origin of the kcat increase with side-chain size for L-amino acid decarboxylation. The specificity of the 2-aminoisobutyrate decarboxylation half-reaction toward oxidative decarboxylation is very high (< 1 in 10(5) turnovers yields nonoxidative decarboxylation). The origin of this specificity is explored with the reactions of amino- and methylaminomalonate. These substrates exhibit high yields of nonoxidative decarboxylation, providing support for a model in which the interaction between a carboxylate group in the B subsite and Arg406 is a prerequisite to proton donation to and removal from C alpha.

Alanine Transaminase↗
PubMed1998

Pre-steady-state kinetic analysis of the reactions of alternate substrates with dialkylglycine decarboxylase.

The pre-steady-state kinetics of the half-reactions of several substrates with dialkylglycine decarboxylase are examined by multiwavelength kinetics and global analysis. The substrates examined fall into two groups: those that exhibit simple, monophasic kinetics and those that exhibit biphasic kinetics. The rate of the AIB half-reaction is likely limited by the decarboxylation step based on the simple kinetics and spectra obtained from global analysis. The spectra for the first species in the transamination half-reactions of L-alanine and L-aminobutyrate show long-wavelength absorption characteristic of a carbanionic quinonoid intermediate. This demonstrates that formation of the external aldimine intermediates and abstraction of the C alpha protons from them are rapid. The reactions of the slower substrates L-phenylglycine and 1-aminocyclohexane-1-carboxylate may have external aldimine formation as the rate-determining step. The biphasic reactions of 2-methyl-2-aminomalonate, 1-aminocyclopentane-1-carboxylate, isopropylamine, and glycine all have external aldimine formation as the rapid observable step, based on the spectral changes observed in absorption and circular dichroism measurements. 2-Methyl-2-aminomalonate reacts approximately 10(4)-fold slower than does AIB with dialkylglycine decarboxylase, compared to approximately 10(5)-fold faster with coenzyme in solution. It is proposed that this radical reactivity reversal is due to a slow protein conformational change that is a prerequisite to decarboxylation of MAM, which occurs rapidly thereafter. Circular dichroism measurements on active site bound coenzyme provide evidence supporting this proposal. The binding of the noncovalent inhibitors pyruvate or lactate or the covalently binding inhibitor 1-aminocyclopropane-1-carboxylate all induce a slow change in coenzyme circular dichroism that quantitatively parallels the slow decarboxylation of 2-methyl-2-aminomalonate. Fast circular dichroism changes are seen in the mixing time of these measurements for both 1-aminocyclopropane-1-carboxylate and 2-methyl-2-aminomalonate, indicating rapid external aldimine formation on this longer time scale.

Aminoisobutyric Acids↗
PubMed1998

IgG antibody levels in the sinus, ear, and airway in a rabbit model of sinusitis with Bacteroides.

OBJECTIVE: To evaluate distribution of IgG antibodies (Ab) in the airway, ear, and sinuses in association with inflammatory changes in a rabbit sinusitis model. DESIGN: We measured IgG Ab and lactate dehydrogenase levels in solutions from sinus, airway, and middle ear lavage and in serum, and determined interferon y messenger RNA expression in sinus and ear mucosa at 1, 2, 3, and 4 weeks after inoculation with Bacteroides fragilis. SUBJECTS: Six rabbits at each time point; controls were untreated (n=5) and sham-operated rabbits at 2 and 4 weeks (n=4-5). INTERVENTION: Bacteroides fragilis was inoculated into the left maxillary sinus with ostium closed. RESULTS: IgG Ab was undetectable in all controls. IgG Ab (>50 microg/g protein) was present at 2, 3, and 4 weeks in most bilateral sinus lavage samples and in 2 of 6, 5 of 6, and 6 of 10 ear lavage samples at 2, 3, and 4 weeks, respectively, following inoculation. Inflammatory changes (histological and lactate dehydrogenase) were much greater in the inflamed sinus. IgG Ab (>50 microg/g protein) was also detected in most bronchoalveolar lavage samples after 2 weeks. Interferon gamma mRNA was undetectable in all untreated and most sham-operated controls but was detected in the bilateral sinus mucosa at 1 to 2 weeks, and remained detectable up to 4 weeks in most rabbits. Serum IgG Ab levels positively correlated with those in lavage samples, with highest correlation with right sinus lavage IgG Ab levels (r=0.56, P<.001). CONCLUSION: IgG Ab levels in the upper airway mucosa likely increase within 2 weeks following bacterial inoculation as a part of mucosal immune responses independent of tissue necrosis.

Animals↗
PubMed1998

Seven novel mutations in mut methylmalonic aciduria.

Methylmalonic aciduria (MMA) is an autosomal recessive inborn error of metabolism that results from functional defects in methylmalonyl CoA mutase (MCM), a nuclear-encoded, mitochondrial enzyme that uses the vitamin B12 derivative, adenosylcobalamin (AdoCbl) as a cofactor. To date, 23 mutations have been identified at the MUT locus on the short arm of chromosome 6, causing the mut forms of MMA (mut complementation group; mut MMA, McKusick #251000). We now report seven novel mutations. Three were found inmut0 patients: R228Q (c759G-->A) was found as a heterozygous change; G312V (c1011G-->T) and 346delL (c1112delCTT) were both found as homozygous changes. Four mutations were found in mut patients: A191E (c648C-->A) and V633G (c1974T-->G) were found in the same patient; 684insL (c2128insCTC) and L685R (c2130T-->G) were both found as homozygous changes. The recent modelling of the human methylmalonyl CoA mutase allowed for an interpretation of the identified mutations.

Alleles↗
PubMed1998

Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15.

Proliferation of memory-phenotype (CD44hi) CD8+ cells induced by infectious agents can be mimicked by injection of type I interferon (IFN I) and by IFN I-inducing agents such as lipopolysaccharide and Poly I:C; such proliferation does not affect naive T cells and appears to be TCR independent. Since IFN I inhibits proliferation in vitro, IFN I-induced proliferation of CD8+ cells in vivo presumably occurs indirectly through production of secondary cytokines, e.g., interleukin-2 (IL-2) or IL-15. We show here that, unlike IL-2, IL-15 closely mimics the effects of IFN I in causing strong and selective stimulation of memory-phenotype CD44hi CD8+ (but not CD4+) cells in vivo; similar specificity applies to purified T cells in vitro and correlates with much higher expression of IL-2Rbeta on CD8+ cells than on CD4+ cells.

Animals↗
PubMed1998

Genetic variation and phylogenetic relationships among six populations of corn borers in China.

The genetic variation among and within six populations of the corn borer was determined by using random amplified polymorphic DNA (RAPD) markers. Extensive genetic variability was detected. Of the 802 RAPD markers obtained, 781 (97.4%) were polymorphic among populations. Genetic similarities and distances between each pair of individuals were calculated. UPGMA cluster analysis showed that the YN population (Ostrinia nubilalis Hübner) and the other five populations (Ostrinia furnacalis Guenée) made up branches of the corn borer lineage, instead of deviating; there was no significant genetic differentiation between YN and the other five corn borer populations.

Animals↗
PubMed1998

Decreases in organ blood flows associated with increases in sublingual PCO2 during hemorrhagic shock.

Earlier studies demonstrated that not only the stomach but also the esophageal wall served as an appropriate site for estimating the severity of circulatory shock by using tonometric methods. We then conceived of the option of sublingual tonometry. In the present study, we tested the hypothesis that the changes in sublingual PCO2 serve as indicators of decreases in blood flow to sublingual and visceral tissue. In Sprague-Dawley rats, sublingual PCO2 increased from 50 to 127 Torr and arterial blood lactate increased from 0.9 to 11.2 mmol/l during bleeding. Sublingual blood flow simultaneously decreased to approximately 32% of preshock values. After reinfusion of shed blood, organ blood flows and sublingual PCO2 were promptly restored to near-baseline values. There were corresponding decreases in blood flows in the tongue, stomach, jejunum, colon, and kidneys during hemorrhagic shock. Increases in sublingual PCO2 were highly correlated with decreases in sublingual blood flow (r = 0.80), tongue blood flow (r = 0.81), gastric blood flow (r = 0.74), jejunal blood flow (r = 0.65), colon blood flow (r = 0.80), and renal blood flow (r = 0.75). Unbled control animals demonstrated no significant changes. Therefore, we anticipate that sublingual tonometry will provide a useful, noninvasive alternative for monitoring visceral PCO2.

Animals↗
PubMed1998

Sublingual capnometry for diagnosis and quantitation of circulatory shock.

We investigated sublingual tissue PCO2 during hemorrhagic and septic shock. Hemorrhagic shock was induced in 10 rats. Sublingual PCO2 increased from 45 to 125 mm Hg and arterial pressure declined from 138 to 49 mm Hg, end-tidal PCO2 decreased from 35 to 13 mm Hg, and cardiac index fell from 290 to 77 ml/min/kg. Arterial blood lactate increased from 0.9 to 15.8 mmol/L. Gastric PCO2 was measured in five animals and it increased from 46 to 87 mm Hg. No significant changes were observed in eight "sham" bled animals including the five animals in which gastric PCO2 was measured. Highly significant linear correlations (p < 0.001) between sublingual PCO2 and gastric PCO2 (r = 0.71), cardiac index (r = -0.74), and arterial lactate (r = 0.59) were documented. We subsequently investigated sublingual PCO2 in five animals in which sepsis was induced by intravenous infusion of live Staphylococcus aureus. Like hemorrhagic shock, highly significant linear correlations were observed between end-tidal PCO2 and cardiac index and between sublingual PCO2 and arterial blood lactate. Sublingual PCO2 promises to serve as a technically simple, noninvasive, and rapid response quantitator of severity of circulatory shock states.

Animals↗
PubMed1998

The effects of hyperoxic injury and antioxidant vitamins on death and proliferation of human small airway epithelial cells.

Previously it was reported that hyperoxia induced death of the human lung adenocarcinoma cell line (A549 cells) by necrosis, not by apoptosis. This study examined proliferation and death of untransformed human small airway epithelial (SAE) cells in normoxia or hyperoxia in comparison with A549 cells. We tested the hypothesis that SAE cells respond differently to hyperoxic injury than do A549 cells. We measured total cell number and viability, thymidine incorporation (SAE cells only), lactate dehydrogenase (LDH) release, and apoptotic changes as markers for cell proliferation and death. Protective effects of antioxidant vitamins also were examined in SAE cells. In normoxia, subconfluent SAE cells had less apoptosis and fewer detached cells, but higher thymidine incorporation than did near-confluent cells. Hyperoxia suppressed thymidine incorporation and augmented apoptosis in both subconfluent and near-confluent SAE cells. Hyperoxia decreased the total cell number only in subconfluence, whereas SAE cell viability declined with hyperoxia in near confluence, but not in subconfluence. For SAE cells, necrosis assessed by LDH release was minimal in all conditions and was not augmented by hyperoxia in SAE cells. In contrast, normoxic A549 cells proliferated more rapidly than did SAE cells with a large number of cells detached during the culture. A549 cells underwent necrotic cell death under confluent or in hyperoxic conditions, but had much less apoptotic cell death. In SAE cells, vitamin E partially prevented the decline of thymidine incorporation with hyperoxia in subconfluence and protected against apoptotic changes with hyperoxia in both subconfluent and near-confluent conditions. Vitamin C prevented apoptosis with hyperoxia only in near-confluent SAE cells. Thus, SAE cells maintained balanced apoptosis and cell proliferation that were altered by cell density and hyperoxia and demonstrated very little necrosis with hyperoxia. Although A549 cells underwent cell death mainly by necrosis, they also were influenced by cell density and hyperoxia. Cell density also determined specific antioxidant vitamin protection in SAE cells.

Antioxidants↗
PubMed1998

Study on delay two-phase multiple organ dysfunction syndrome.

OBJECTIVE: To study the injury factors, pathogenic process and clinical features of delay two-phase multiple organ dysfunction syndrome (MODS) in severe burned patients and to replicate a standardized animal model that would accurately imitate the clinical features of MODS. METHODS: Forty-five human patients with burn size larger than 30% total body surface area (TBSA) were analyzed. All of them underwent severe burn shock in early stage and sepsis in late stage. Thirty-two goats were randomly divided into three groups: 1) hemorrhagic shock (group H, n = 6); 2) endotoxemia (group E, n = 6); and 3) hemorrhagic shock plus endotoxemia (group M, n = 20). Hemorrhagic shock was produced according to the method of Wigger (6.7 kPa for an hour, 1 kPa = 7.5 mmHg). Endotoxin (E. coli O111 B4) was given via the portal vein 24 hours after the resuscitation of hemorrhagic shock, in a dose of 30 ng/kg/min for 5 consecutive days. During the observation period of 10 days, all animals were hemodynamically monitored, given standard metabolic support and due cardiac and pulmonary support according to human intensive care. RESULTS: All the patients showed burn shock at 1-3 days and hyperdynamic circulation, hypermetabolism and systemic inflammatory responses over two weeks post-injury. Thirteen cases were found to develop MODS according to the prevailing diagnostic criteria, and 10 of them died with a mortality of 77%. Eighteen animals died in group M with a mortality of 90%, 12 of the 18 developed MODS, with overall incidence of 60%. Most animals in group M showed changes similar to that observed in human cases. The experimentation proved that in the pathogenic process of MODS, there was a two-hit phenomenon in the dvelopment of the syndrome. To prevent the development of MODS, it therefore was imperative to blunt the first hit or the second hit, so that an excessive inflammatory response was alleviated. This postulation has been verified in the treatment of extensive burns. Two patients with burn extent reaching 100% TBSA survived with only mild acute respiratory distress syndrome (ARDS) and renal dysfunction after comprehensive treatment of burn shock, including adequate fluid resuscitation, drugs to remove oxygen free radicals, rapid restoration of pHi, and early extensive excision of burn eschars. CONCLUSION: Both in human patients or animal experimentation, the typical delay two-phase MODS is shown to be produced by two successive insults in the forms of hypovolemic shock and sepsis. This postulation is helpful in formulating the prevention and treatment modality of MODS.

Adult↗
PubMed1998

[Influence of escharectomy during burn shock stage upon the changes in endothelin and NO].

OBJECTIVE: To observe influence of escharectomy during and after burn shock stage upon the changes in plasma ET and NO. METHODS: 35% TBSA full-thickness burn was produced in pigs, which were divided into two groups. Group S was a group undergoing escharectomy during burn shock stage at 24 h postburn. Group C was a group receiving escharectomy at 96 h after injury. ET and NO were determined and ET/NO was calculated. RESULTS: The levels of ET and NO were higher after injury than before injury in both groups. The level of ET was lower significantly in group S than in group C from 96 h postburn on. The level of NO was higher in group S than in group C. The ET/NO was lower in group S than in group C from PBH 24 on. CONCLUSION: Escharectomy during burn shock stage was beneficial in reducing injury of endothelial cells, decreasing exudation and edema, decreasing tissue hypoxia and improving microcirculation.

Animals↗
PubMed1998

[The effect of certain pro-inflammatory mediators on the pathogenesis of acute gastric mucosal lesion in early burn stage].

OBJECTIVE: To appraise the effect of certain pro-inflammatory mediators on the pathogenesis of acute gastric mucosal lesion in early burn stage. METHODS: 21 patients with burn injuries of over 30% TBSA were divided into A and B groups according to the main clinical indexes during shock resuscitation and hemodynamic parameters. Fiberoptic endoscopic examination, determination of intramucosal pH (pHi) and measurement of some mediators were done immediately after admission to the hospital and 4 and 7 days after burn injury. RESULTS: It was demonstrated that the level of LPS in plasma, the content of TNF-alpha, IL-8 and ET in group B at 4 and 7 days postburn were significantly higher than those of group A, while the value of pHi in group B was markedly lower than that of group A. Damaging index of gastric mucosa was negatively correlated with pHi (r = -0.89, P < 0.05), but positively with ET (r = 0.91, P = 0.05). CONCLUSIONS: These findings suggest that the inflammatory mediators and cytokines promoted secondary damage to gastric mucosa during early postburn. It was believed that pHi was a sensitive index, and it played an important role in the development of stress ulceration.

Adolescent↗
PubMed1998

[Blood supply reestablishment of avascular necrosis of femoral head with digital subtraction angiography].

OBJECTIVE: To use digital subtraction angiography (DSA) to evaluate blood supply reestablishment after the treatment of the avascular necrosis of femoral head (ANFH) by using the vascularized iliac periosteum with deep iliac circumflex artery (DICA) and vein pedicle. METHODS: Seldinger method was used to puncture femoral artery interpate of 20 patients with pre and postoperative ANFH. 6.5 F Cobrn conduct was optionally used and put directly into DICA and then contrast medium, was injected for observation of blood vessel. RESULTS: Before operation, the position of DICA was found constant, 3 to 7 branches termity among the crest part of iliac bone. Three weekes after operation, DICA was found wider than that before operation, but the blood flow speed remained almost the same and its termity was distributed evenly inside the femoral head and looked like a bird's net. Three months after operation, the blood vessel was still wider, but blood flowed faster and its termity changed roundish, and the bird's net changed greatly and capillaries reached the subchoronal zone of femoral head. CONCLUSION: Blood flow was well reestablished after the treatment of ANFH by DSA. It can be easily checked with less damage, large liability, and clear picture.

Adult↗
PubMed1998

[The effect of tamoxifen on experimental nasal hypersensitivity].

The effect of estrogen on nasal hypersensitivity was observed in female adult guinea pigs with high level of estrogen. The animal were divided into three groups: group A as normal control; in group B, tamoxifen was given before inducing high level estrogen and in group C, estrogen was given but without tamoxifen. The groups B and C were sensitized and then challenge with TDI as described previously. The result showed that tamoxifen may inhibit significantly the development of nasal hypersensitivity and reduce the pathologic changes of nasal mucosa. It is suggested that the mast cells may be the target of estrogen and tamoxifen might be useful in treatment of nasal hyperreaction concerning with the change of estrogen level.

Animals↗