Search PubMed⌕ Search

Biomedical subjects

X Sun

Publications and source records attributed to X Sun.

At least 541 records · Page 30Linked to original sources
PubMed1992

Xanthine oxidase/hydrogen peroxide generates sulfur trioxide anion radical (SO3.-) from sulfite (SO3(2-)).

In the presence of hydrogen peroxide (H2O2), xanthine oxidase has been found to catalyze sulfur trioxide anion radical (SO3.-) formation from sulfite anion (SO3(2-)). The SO3.- radical was identified by ESR (electron spin resonance) spin trapping, utilizing 5,5-dimethyl-l-pyrroline-l-oxide (DMPO) as the spin trap. Inactivated xanthine oxidase does not catalyze SO3.- radical formation, implying a specific role for this enzyme. The initial rate of SO3.- radical formation increases linearly with xanthine oxidase concentration. Together, these observations indicate that the SO3.- generation occurs enzymatically. These results suggest a new property of xanthine oxidase and perhaps also a significant step in the mechanism of sulfite toxicity in cellular systems.

Electron Spin Resonance Spectroscopy↗
PubMed1992

Borrelia burgdorferi strain 25015: characterization of outer surface protein A and vaccination against infection.

Mice vaccinated with outer surface protein A (OspA) from Borrelia burgdorferi strain N40 are protected from challenge with an intradermal syringe inoculum of B. burgdorferi strains N40, B31, and CD16. Vaccination experiments were done to determine if protection extended to strains 297 and 25015. We now show that OspA-N40 immunized mice are protected against challenge with strain 297, isolated from the cerebrospinal fluid of a patient with neuroborreliosis, but not against challenge with strain 25015, isolated from a tick in Millbrook, NY. The OspA gene from strain 25015 was therefore cloned and sequenced. The deduced OspA-25015 protein sequence differs from OspA-N40 at 40 of 273 amino acids. Furthermore, mice vaccinated with rOspA-25015 are protected from challenge with strain 25015 but not against strain N40. The results extend the usefulness of OspA as a vaccine candidate, but indicate that OspA can vary among strains of B. burgdorferi and that vaccination of mice with OspA-N40 does not protect against intradermal challenge with an inoculum of 10(4) strain 25015 spirochetes.

Amino Acid Sequence↗
PubMed1992

Selective potentiation of NMDA-induced activity and release of excitatory amino acids by dynorphin: possible roles in paralysis and neurotoxicity.

Selective antagonists of N-methyl-D-aspartate (NMDA) excitatory amino acid (EAA) receptors have been shown to protect against dynorphin-A (DYN)-induced paralysis and neurotoxicity in the spinal cord. To test the hypothesis that either DYN-induced paralysis or neurotoxicity involves an enhanced release of EAAs, we used microdialysis to monitor aspartate (Asp) and glutamate (Glu) release in both the lumbar spinal cord extracellular fluid (ECF) and the spinal cord cerebral spinal fluid (CSF) of conscious rats in response to DYN (1-13). Injection of 5 nmol of DYN produced temporary paralysis in 8 of 10 animals, but did not significantly change Asp or Glu release in either the ECF or the CSF. Injection of 20 nmol of DYN caused permanent paralysis and neuronal cell loss in all animals tested as well as a significant increase of Asp and Glu in both the ECF and the CSF, and a decrease in glutamine (Gln) release only in the ECF. Pretreatment with 1 mg/kg of the NMDA antagonist MK-801 blocked both paralysis and amino acid changes in the ECF. Pretreatment of animals with 5 mg/kg naloxone inhibited glutamate release in the ECF, but did not block paralysis, Asp release or inhibition of Gln release. As MK-801 sensitive paralysis by DYN was not mediated through enhanced EAA release, we examined whether DYN could act through postsynaptic facilitation of NMDA receptors by testing the ability of DYN to alter the magnitude of a behavioral response produced by intrathecal injection of NMDA in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Electroretinographic oscillatory potentials in diabetic retinopathy. An analysis in the domains of time and frequency.

The oscillatory potentials of the electroretinogram in dark and light adaptation were evaluated by Fourier transform in 87 diabetics and 74 age-matched controls. The study consisted of four groups: normal control, no observable diabetic retinopathy, background diabetic retinopathy and proliferative diabetic retinopathy. A reduction in the amplitude of each oscillatory potential, the summed amplitudes, the area and the total power of the oscillatory potentials as well as delayed implicit time of each oscillatory potential peak in dark and light adaptation could be found in patients with background diabetic retinopathy and proliferative diabetic retinopathy. The amplitude of oscillatory potential 4 in dark adaptation and the total power of the oscillatory potentials in light adaptation seemed to be affected in patients with no observable diabetic retinopathy. The implicit time of oscillatory potential 2 in dark adaptation was valuable to distinguish between patients with no observable diabetic retinopathy and background diabetic retinopathy.

Adult↗
PubMed1992

Antinociceptive effects of intrathecal taurine and calcium in the mouse.

Taurine (Tau), calcium (Ca+2) and opiates each produce antinociception when injected i.t. in mice. This study was initiated to determine whether there is a common mechanism underlying their antinociceptive effects. Using the abdominal stretch assay, the antinociceptive effects of both Tau (12 nmol) and Ca+2 (72 nmol) were antagonized by i.t. TAG (4.4 nmol), a Tau antagonist, but not by i.p. injection of the opiate antagonist naloxone (5 mg/kg). The antinociceptive effects of Tau and Ca+2 correlated with their ability to inhibit the intensity of caudally-directed biting and scratching behaviors produced by i.t. NMDA or kainic acid. The inhibitory effects of both Tau and Ca+2 on the biting and scratching behaviors behaviors induced by substance P or excitatory amino acids were reversed by TAG, suggesting a common mediation by Tau. These data indicate that the antinociceptive effects of both Tau and Ca+2 appear to be mediated, at least in part, by Tau but not by the release of endogenous opioid compounds. In addition, inhibition of chemical irritant-induced nociception may be produced by a simple blockade of excitatory amino acid activity.

Amino Acids↗
PubMed1992

Effects of sized heparin oligosaccharide on the interactions of Chinese hamster ovary cell with thrombospondin.

Binding and degradation of TSP by CHO cells and adhesion of CHO cells to substrate-adsorbed TSP are mediated by cell surface PGs and inhibitable by heparin. In order to learn how these three processes are related, we studied the effects of defined heparin oligosaccharides up to 18-mer produced by nitrous acid digestion. There was a complex correlation among oligosaccharide chain length, affinity of oligosaccharide for TSP in a solid phase binding assay, and potencies of oligosaccharide in inhibition of the three cellular processes. Inhibition of degradation was more sensitive to shorter oligosaccharides than inhibition of binding. For instance, the 10-mer inhibited binding of TSP to cells by 10% and degradation by 70%. Punctate immunofluorescence of cell surface bound TSP was replaced by a diffuse pattern after incubation in the presence of the 10-mer. These results suggest that the clustering of TSP on the cell surface may trigger endocytosis and degradation. Inhibition of binding of TSP to cells, in turn, was more sensitive to midsized oligosaccharides than inhibition of cell adhesion to adsorbed TSP. Inhibition of adhesion correlated with the ability of oligosaccharides to block binding of 125I-heparin to adsorbed TSP.

Adsorption↗
PubMed1992

Disulfides modulate RGD-inhibitable cell adhesive activity of thrombospondin.

Thrombospondin (TSP) contains the Arg-Gly-Asp (RGD) sequence that is thought to be important for cell adhesion mediated by several cell-surface integrin receptors. The RGD sequence is located in the type 3 repeat region of TSP that has multiple Ca2+ binding sites and is subject to a complex intramolecular thiol-disulfide isomerization. TSP that we isolated from thrombin-activated human platelets using buffers containing 0.1 mM Ca2+, in which Cys974 is the major labeled cysteine, did not have RGD-inhibitable adhesive activity. However, one of our preparations of TSP and TSP purified following alternative procedures using greater than or equal to 0.3 mM Ca2+ did have RGD-inhibitable adhesive activity. Reduction of TSP with DTT, either before or after adsorption to surfaces, enhanced its adhesive activity. Reduced TSP supported robust cell spreading when coated at concentrations as low as 1 micrograms/ml, whereas "adhesive" TSP not treated with DTT was active at coating concentration of greater than 20 micrograms/ml and supported only modest cell spreading. Lower DTT concentrations were required for enhancement of the adhesive activity of TSP if Ca2+ was chelated with EDTA. Cellular adhesion to DTT-treated TSP was inhibited by RGD-containing peptide and by mAb to a functional site of the alpha v beta 3 integrin. Cell blots of reduced proteolytic fragments of TSP localized the adhesive activity to the RGD-containing type 3 repeat region. These results suggest a novel mechanism for regulation of integrin-ligand interactions in which the ligand can isomerize between inactive and active forms.

Amino Acid Sequence↗
PubMed1992

Apolipoprotein gene expression in analbuminemic rats and in rats with Heymann nephritis.

The nephrotic syndrome results from altered glomerular permselectivity, causing urinary protein loss, reduced albumin concentration, oncotic pressure (pi), and hyperlipidemia. Hepatic lipid and apolipoprotein synthesis increases and lipoprotein catabolism decreases. Decreased lipoprotein catabolism follows the onset of proteinuria but is not associated with hereditary analbuminemia [Nagase analbuminemic rat (NAR)] if proteinuria is absent. We measured plasma apolipoproteins (apo) AI, B, and E levels, their mRNA concentrations in liver, and the transcription rate of each mRNA in rats with Heymann nephritis (HN) or NAR to determine which alterations occurred in NAR alone without proteinuria. Plasma apo AI, B, and E were increased in both HN and NAR. Cholesterol and apo AI were inversely proportional to pi and independent of urinary protein loss or the presence of albumin in plasma. In contrast, triglycerides (TGs) were significantly greater in HN and were increased out of proportion to apo B. The concentration of apo AI mRNA increased in liver of both HN and NAR as did apo AI transcription. Apo E mRNA increased in neither HN nor NAR, whereas apo B mRNA increased only in HN. Transcription of neither apo B nor E increased. Plasma apo AI levels are likely to be regulated transcriptionally at the level of protein synthesis, whereas plasma apo B and E levels are regulated either posttranscriptionally, at the level of protein catabolism, or at both sites. Lipoproteins rich in TG and poor in apo B appear after the development of proteinuria but not as a consequence of analbuminemia alone. The accumulation of TG-rich apo B containing lipoproteins in rats with HN may result from impaired lipolysis occurring as a consequence of proteinuria.

Animals↗
PubMed1992

Patterns of sedation and analgesia in the postoperative ICU patient.

Control of pain, discomfort, and agitation is an integral part of the postoperative management of critically ill patients. We examined the sedative and analgesic practices in a surgical ICU during two six-month periods, one in 1986-1987 and the other in 1989-1990. Narcotics, especially morphine and Fentanyl, were the most commonly used drugs. The amount of Fentanyl received by the endotracheal patients in the 1986-1987 group was quite large, 5.5 +/- 4.3 (SD) mg/day. The use of midazolam during the second survey period was associated with a reduced dose of narcotics in artificially ventilated patients receiving continuous intravenous Fentanyl and morphine. The use of epidural Fentanyl, especially following thoracic surgery, was greatly increased during the second study period. More work is needed to assess the effects and effectiveness of ICU sedative and analgesic regimens.

Adult↗
PubMed1992

Evaluation of definitions for sepsis.

OBJECTIVE: To evaluate the current definitions for sepsis and clarify and quantify the risk for intensive care unit (ICU) patients with sepsis. DESIGN: A prospective cohort analysis of 519 patients with a primary clinical diagnosis of sepsis treated in the ICUs of 40 US hospitals drawn from a nationally representative sample of 17,440 admissions. MEASUREMENTS: Patient's age, treatment location prior to ICU admission, comorbidities, origin of sepsis, daily physiologic measurements, therapeutic intensity, and subsequent hospital mortality rate. INTERVENTION: Patients were categorized into subgroups by important risk factors and into current clinical definitions of sepsis. Patients also were provided an individual risk of hospital mortality based on their individual predicted risk by using the first ICU day APACHE III score, treatment location prior to ICU admission, and etiology of sepsis. RESULTS: Patients with a designated urinary source of sepsis had a significantly lower baseline risk of death (30 percent) than patients with other causes (54 percent, p less than 0.01). Patients admitted to the ICU from the emergency department also had significantly lower mortality (37 percent) than patients admitted from hospital wards, other units within the hospital, or transferred from other hospitals (55 percent, p less than 0.01). Recognized definitions such as "sepsis syndrome" and "septic shock" identified groups of patients with significantly different mortality rates, 40 percent and 64 percent, respectively (p less than 0.01), but the range of individual patient risks within these groups were indistinguishable from the 211 patients (41 percent) that did not meet these definitions during the initial seven days of ICU treatment. Multivariate analysis using initial APACHE III score, etiology (urosepsis or other), and treatment location prior to ICU admission provided the greatest degree of discrimination (ROC = 0.82) of patients by risk of hospital death. CONCLUSIONS: Sepsis is a complex clinical entity and could be viewed as a continuum with substantial variation in initial severity and risk of hospital death. One accurate description of sepsis is the continuous measure of hospital mortality risk estimated primarily from physiologic abnormalities.

Bacteremia↗
PubMed1992

Amino terminus of substance P potentiates kainic acid-induced activity in the mouse spinal cord.

Sensitization to the behavioral effects produced by repeated injections of kainic acid (KA) into the mouse spinal cord area has been previously shown to be abolished by pretreatment with capsaicin, a neurotoxin of substance P (SP)-containing primary afferent C-fibers. While SP has a variety of well characterized biological actions that are mediated by interactions of its COOH terminus with neurokinin receptors, more recently we have characterized an amino-terminally directed SP binding site. The present studies were initiated to determine whether behavioral sensitization to repeated injections of intrathecally administered KA is mediated by the COOH or NH2 terminal of SP. In the present studies, pretreatment with SP(1-7), an NH2-terminal fragment of SP, but not SP(5-11), a COOH-terminal fragment, potentiated KA-induced behavioral activity in mice. Pretreatment with [D-Pro2,D-Phe7]SP(1-7), an inhibitor of SP NH2-terminal binding, blocked the potentiative effect of SP(1-7) as well as the sensitization to repeated injections of KA. In contrast, [D-Pro2,D-Trp7,9]SP, a neurokinin antagonist, had little effect on behavioral sensitization to KA. The present study suggests that SP has an important modulatory role on excitatory amino acid activity in the spinal cord that is mediated by an action of the NH2 terminal of SP at a non-neurokinin receptor.

Animals↗
PubMed1992

Peptides as targets for antihypertensive drug development.

AIM: To assess the potential for development of new classes of pharmacological drugs in the treatment of hypertension and cardiovascular disease. BACKGROUND: Basis of pharmacological blood pressure reduction: Since the discovery of the renin-angiotensin system by Tigerstedt almost 100 years ago, a large number of vasoactive peptides have been discovered. By interaction with such peptides of endocrine, perivascular or endothelial origin, blood pressure may be modulated. BLOCKADE OF THE RENIN-ANGIOTENSIN SYSTEM: The success of the angiotensin converting enzyme (ACE) inhibitors in hypertension and congestive heart failure is generally attributed to reduced generation of angiotensin II. The recent development of specific and highly potent Ang II type 1 subtype receptor antagonists such as losartan (DuP753, MK954) have provided a new opportunity to inhibit the renin-angiotensin system, and this is currently being explored in hypertensive patients. In addition, blockade of the first and rate-limiting reaction of the renin-angiotensin system, inhibition of renin activity, is also a target for the development of antihypertensive drugs. However, this development is hampered at present by a compensatory increase in active renin that clinically offsets the antihypertensive action of renin inhibitors. PHARMACOLOGICALLY INDUCED INCREASE IN ATRIAL NATRIURETIC PEPTIDE (ANP): The availability of circulating or tissue ANP may be increased by inhibiting its metabolic clearance by NEP-24.11 inhibitor drugs. These agents induce a reduction in blood pressure and diuretic effects in animal models, and may become a new class of drugs for the clinical management of patients with hypertension and congestive heart failure. OTHER POTENTIAL PHARMACOLOGICAL TARGETS IN THE MANAGEMENT OF HYPERTENSION: There are several potential pharmacological targets that may lead to the development of novel antihypertensive agents in the future. These include the interaction or blockade of vasopressor peptides. Routes of development include neuropeptide Y1 receptor antagonists, which block the postjunctional vasopressor effect of neuropeptide Y, or endothelin antagonists, which block endothelin pressor actions at the endothelin A receptor site. The cardiovascular actions of the functional neuropeptide Y inhibitor alpha-trinositol (PP 56) provide a potential new mechanism for reducing blood pressure in hypertension. In addition, the recent discovery of small molecular agents with high potency and specificity for the endothelin A receptor subtype may also be of value in specific vascular disease states. CONCLUSIONS: Future development is likely to provide us with novel drugs based on interactions with vasoactive peptides that may improve the management of specific cardiovascular disease states.

Amino Acid Sequence↗
PubMed1992

[Prognostic significance of DNA content in transitional cell carcinoma of the urinary bladder].

The cellular DNA content in paraffin-embedded specimens of recurrent transitional cell carcinoma of the urinary bladder were analyzed by quantitative image analysis in 48 and flow cytometry techniques in 44 cases. The results showed a positive correlation of cellular ploidy with malignant proliferation of the tumors. The aneuploidy was increased in cases of higher clinical stages and histological grades. The prognosis of patients with diploid cells was better than those with aneuploidy, while patients with aneuploidy and higher grading showed very poor prognosis. The recurrence rate of diploid tumors was considerably lower than that of aneuploid tumors. The results indicate that such a correlation might be of clinical significance in prognosis and predicting and controlling recurrence of tumors.

Adult↗