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Biomedical subjects

K Sun

Publications and source records attributed to K Sun.

At least 163 records · Page 9Linked to original sources

Genomic structure and chromosomal localization of processed pseudogenes for human RBP-Jk.

The functional gene for human recombination signal sequence-binding protein (RBP-Jk) and corresponding processed psudogenes have been isolated from various species, such as Drosophila, Xenopus, mouse, and human. Here we report the isolation of another two genomic pseudogenes of human RBP-Jk, named K2 and K7, from a cosmid library of Hela cells. The nucleotide sequences of both genes exhibited more than 95% homology to the functional human gene for RBP-Jk. Moreover, they did not contain any intron sequences and were interrupted by several stop codons in all frames. In situ hybridization demonstrated that the pseudogenes, K2 and K7, were localized at chromosomes 9p13 and 9q13, respectively. Their physical maps differed from those of the true functional gene and of the pseudogenes reported previously by Amakawa et al. (1993).

Base Sequence↗

Effect of exercise supplementation during adenosine infusion on hyperemic blood flow and flow reserve.

Physical stress might modulate myocardial blood flow in near-maximally dilated coronary arteries by increasing coronary perfusion pressure, myocardial contractility, and heart rate. The net effect of these changes on hyperemic blood flows has not yet been defined in humans. To quantify the effect of physical exercise on pharmacologically induced hyperemia, myocardial blood flow was measured in 11 healthy volunteers. Measurements were performed with positron emission tomographic imaging with nitrogen-13 ammonia at rest, during intravenous (i.v.) adenosine administration (140 micrograms.kg-1.min-1 over 6 minutes), and during i.v. adenosine administration plus supine bicycle exercise with a maximal workload of 125 W. Myocardial blood flow was quantified by using a previously validated graphic analysis. Heart rate, systolic blood pressure, rate-pressure product, and mean aortic blood pressures were significantly higher during combined physical and pharmacologic stress than during pharmacologic stress alone. However, myocardial blood flow decreased from 2.6 +/- 0.4 to 2.2 +/- 0.4 ml.min-1.gm-1 with the addition of physical stress (p < 0.05). This decline was associated with a significant increase in coronary vascular resistance (35 +/- 6 vs 52 +/- 13 mm Hg.ml-1.gm.min; p < 0.05). Accordingly, myocardial flow reserve declined, from 5.0 +/- 0.9 to 4.3 +/- 1.0, with exercise supplementation (p < 0.05). Exercise in addition to pharmacologic stress increases coronary vascular resistance and thus significantly decreases hyperemic myocardial blood flow and flow reserve. This decrease results most likely from an increase in extravascular restrictive forces caused by higher ventricular pressures and contractility during physical stress.

Adenosine↗

Omega-3 and omega-6 fatty acids and PGE2 stimulate the growth of normal but not tumor mouse mammary epithelial cells: evidence for alterations in the signaling pathways in tumor cells.

The direct effect of omega-3 and omega-6 fatty acids on the proliferation of mouse mammary tumor cells (MTC) was examined in a serum-free cell culture system. While the EGF-induced proliferation of normal mammary epithelial cells was shown to be enhanced by omega-3 and omega-6 fatty acids and prostaglandins (PGs), a majority (75-80%) of primary mammary tumors were not stimulated by these agents. Compared to normal cells, some MTC cultures showed a higher susceptibility to inhibition by omega-3 fatty acids. The general lack of response of MTC cultures to PGE2 and cyclic adenosine monophosphate (cAMP) suggests some alterations in the cAMP-mediated pathway. However, the PGE2-induced cAMP levels and cAMP-dependent protein kinase (PKA) activities in the tumor cells were comparable to normal cells. We conclude that the proliferation of mammary tumor cells either follow a cAMP-PKA-independent pathway or have some alterations in the serine/threonine kinase mediated signaling pathway.

1-Methyl-3-isobutylxanthine↗

Basal and KCl-stimulated corticotropin-releasing hormone release from human placental syncytiotrophoblasts is inhibited by sodium nitroprusside.

Human placenta synthesizes and secretes large amounts of CRH during the second and third trimesters. In the hypothalamus, nitric oxide (NO) has been reported to affect CRH release. We studied the effect of NO on the regulation of placental CRH secretion. The effect of the NO donor sodium nitroprusside (SNP) on basal and KCl-stimulated CRH release was examined in cultured human syncytiotrophoblasts. CRH secretion and intracellular concentrations of cGMP, calmodulin-dependent protein kinase (CaM-PK), protein kinase-G (PKG), protein kinase-C, and cAMP-dependent protein kinase holoenzyme were measured under basal conditions and after treatment with a depolarizing concentration of KCl and with SNP. The results showed that depolarization (3 h) increased CRH release 4-fold (from basal value of 5.16 +/- 0.65 to 19.31 +/- 4.46 fmol/10(6) cells); SNP (100 mumol/L) decreased both basal (0.42 +/- 0.21 fmol/10(6) cells) and KCl-stimulated CRH release (0.94 +/- 0.32 fmol/10(6) cells). KCl also increased the activity of CaM-PK in the cell membrane and both cytosolic and membrane PKG activity, whereas the activities of protein kinase-C and cAMP-dependent protein kinase holoenzyme were unchanged. SNP increased intracellular cGMP concentrations after 10, 60, and 180 min. Methylene blue (100 mumol/L), a guanylate cyclase inhibitor, blocked the inhibitory effects of SNP on CRH release. These results suggest that NO exerts inhibitory effects on both basal and KCl-stimulated CRH release from placental syncytiotrophoblasts through a cGMP-mediated pathway. In addition, as KCl-induced changes in the cell membrane were blocked by SNP, CaM-PK may be involved in KCl-stimulated CRH release. KCl may also sensitize the inhibitory pathway involved in the regulation of CRH release by increasing cellular PKG levels. The effects of KCl and SNP on CRH release are more complex than simple activation of CaM-PK and PKG activity, as other cellular signal transduction pathways are also modulated.

Calcium-Calmodulin-Dependent Protein Kinases↗

Cognitive performance in a high-functioning community-dwelling elderly population.

BACKGROUND: The purpose of this study was to examine the role of demographic factors as predictors of cognitive performance in a high-functioning, community-dwelling elderly population. METHODS: The study cohort consisted of 1,192 community-dwelling subjects, who were selected to represent the highest third of an elderly population with respect to physical and cognitive functioning. A neuropsychological battery, including 5 cognitive performance subtests (confrontation naming, delayed recognition span, similarities, figure-copying, and incidental delayed recall) was administered to the subjects in their homes. RESULTS: A summary measure of the 5 neuropsychological subtest scores, the total cognitive score, arrayed the study group across a broad range of difficulty, creating a near-normal distribution. Education, income, and race had statistically significant associations with the total score and the individual subtests. The effect of education was the most striking finding, explaining 30% of the variance in the total score. Education was most strongly related to the abstraction (partial R2 = .11) subtest, and least related to the memory subtests, delayed recognition (R2 = .02) and delayed recall (R2 = .01). CONCLUSIONS: Demographic factors are important predictors of cognitive performance in this high-functioning cohort. Education had the strongest influence on overall cognitive performance, and particularly notable associations with subtests that depended upon the use of previously learned materials. Longitudinal follow-up, now underway, will help to determine whether high levels of education help to maintain cognitive performance with age.

Aged↗

Technology assessment in diagnostic imaging. A proposal for a phased approach to evaluating radiology research.

RATIONALE AND OBJECTIVES: The authors propose an objective basis for critical evaluation of research trends and define and analyze a sample of radiology studies according to research phase. METHODS: A random sample of 146 original diagnostic studies from two radiology journals was categorized according to phase, modality, and design by three physician reviewers, collated with a microcomputer database, and analyzed using an SAS program. RESULTS: Phase 1 studies (technical evaluation) constituted 18.5% of publications: phase 2 (standardization and tissue characterization), 10.3%; phase 3 (spectrum of appearances), 40.4%; phase 4 (diagnostic efficacy), 21.2%; and phase 5 (clinical evaluation), 9.6%. Of 48 diagnostic efficacy studies, 42% were prospective (versus 35% for the total sample), 38% were controlled (median sample size, 53 [versus 30 for the total sample]). Only 27% of the 48 diagnostic efficacy studies were externally funded. Research in magnetic resonance imaging (MRI), which comprised 45% of all publications, was oriented toward phase 1 (32%) rather than phase 5 studies (0%). Phase 5 studies were the focus of 18% and 8% of ultrasound (US) and computed tomography (CT) studies, respectively. There were more prospective, controlled efficacy studies in US than in MRI or CT. CONCLUSIONS: Analyses of research trends will be facilitated by use of a standard taxonomy which adopts a modality-based, phased approach.

Diagnostic Imaging↗

[Length method in evaluating right ventricular volume in children with congenital heart disease: a comparison with two dimensional echocardiographic method].

The accuracy and reliability of two-dimensional echocardiographic length method in right ventricular volume measurement were assessed by three-dimensional echocardiographic method in 10 normal children, 10 patients with atrial septal defect, and 10 patients with pulmonary stenosis. Their age and sex were matched. Right ventricular end diastolic, end systolic, mid-systolic volume, and ejection fraction evaluated by length method were correlated very well with the values obtained by three-dimensional echocardiographic method in normal and pulmonary stenosis group (r = 0.71-0.95, P < 0.01). In atrial septal defect group, right ventricular volume obtained by the two methods was correlated well (r = 0.86-0.95, P < 0.01). Although the correlation in right ventricular ejection fraction was lower, it was still significant. The shortening rate of X, Y, Z parameters required by length method were similar in each group: delta Z % > delta X % > delta Y %. We conclude that right ventricular volume and function could be assessed accurately by two-dimensional echocardiographic length method in children with right ventricular volume or pressor overloaded, and that right ventricular systolic pattern is similar in those situations.

Child, Preschool↗

Unscheduled DNA synthesis induced by the antitumor drug vincristine in germ cells of male mice.

The cytotoxic and genotoxic effects of vincristine (VCR) on germ cells of male mice were investigated. Several parameters (the scale and the time course of unscheduled and scheduled DNA synthesis in spermatocytes and spermatids and the number of sperm present in caudal epididymides) were analyzed. Our results show that intraperitoneal administration of a single dose of VCR resulted in: (1) damage to DNA in spermatocytes and spermatids; (2) a reduction in the rate of germ-cell development; and (3) killing of the non-proliferating spermatid cells. Damage of DNA in germ cells indicates that VCR may have potential genetic hazards to patients who receive it in antitumor therapy.

Animals↗

[Stability of shuang huanglian aerosol].

The contents of chlorogenic acid and baicalin in shuang huanglian aerosol were determined by HPLC. The process of chemical kinetics of the aerosol was studied by constant temperature acceleration tests, and the stability of the drug predicted. The results appeared close to those from the stored sample method. pH changes during degradation of the drug were also observed.

Aerosols↗

Comparison of selective arginine vasopressin V1 and V2 receptor antagonists on burn shock in the rat.

STUDY OBJECTIVE: Two selective V1 and V2 receptor antagonists of arginine vasopressin, d(CH2)5Tyr(Me)AVP and d(CH2)5[D-Ile2, Ile4, Ala9-NH2]AVP, were given intravenously in burn shocked rats to investigate the respective effects of V1 and V2 receptor blockade on the haemodynamic variables in burn shock. DESIGN: Computer assisted on line real time measurements of mean arterial blood pressure, diastolic blood pressure, left ventricular systolic pressure, dP/dtmax, and heart rate were used to study the effects of the receptor antagonists during burn shock. In addition, the radioactive microsphere method was used to measure the changes of cardiac output and regional blood flows to heart, kidney, and liver in response to the antagonists during burn shock. Third degree burns extending over 30% of body surface area were made by dipping the rat's shaved back into water at 100 degrees C for 20 s. EXPERIMENTAL MATERIAL: Male Sprague-Dawley rats (250-300 g) were used in groups of 6-9 per experiment. MEASUREMENTS AND MAIN RESULTS: Mean and diastolic arterial blood pressures, left ventricular systolic pressure, dP/dtmax and heart rate were measured for 8 h after burns. Cardiac output and regional blood flow were measured at 3 h and 8 h postburn. Results showed that blockade of V1 receptor lowered mean and diastolic arterial blood pressures throughout the 8 h period, and raised left ventricular systolic pressure and dP/dtmax only during the early phase of shock. Cardiac output and blood flows to heart, kidney, and liver were increased by the V1 antagonist at 3 h but not at 8 h postburn. The V2 receptor antagonist increased mean and diastolic arterial blood pressures, left ventricular systolic pressure, and dP/dtmax both during the early and during the late phases of burn shock. It also improved cardiac output and blood flows to the heart, kidney, and liver during the early and late phases of burn shock. However, heart rate was not affected by V1 and V2 receptor antagonists. CONCLUSIONS: The V2 like receptor may be the dominating receptor mediating vasopressin's inhibitory effect on the heart. V1 receptor mediated coronary vasoconstriction contributes to the myocardial depression possibly only at the compensatory phase of shock. In addition V1 receptor mediated vasoconstriction is important in maintaining blood pressure during burn shock.

Angiotensin Receptor Antagonists↗

Inhibition of methyl methanesulfonate-induced unscheduled DNA synthesis in spermatozoa of mice by Poly I-C.

Methyl methanesulfonate (MMS 75 mg.kg-1)-induced unscheduled DNA synthesis (UDS) was inhibited significantly in the spermatozoa of mice injected with Poly I-C (0.05, 0.50, and 5.00 mg.kg-1) at 4 h prior to ip MMS. Radioactivity was reduced from 53 +/- 3 to 50, 45 +/- 5, and 34 +/- 6 dpm/million sperms respectively. The effects of Poly I-C were dose-dependent (r = 0.9498, P less than 0.05) in inhibition of MMS-induced UDS. The effect of serum collected from the mice injected with Poly I-C (0.50 mg.kg-1) had similar effects as that of Poly I-C. Our findings suggest that both Poly I-C alone and mouse serum induced with Poly I-C may prevent the DNA damage produced by MMS.

Animals↗

Effect of peripheral injection of arginine vasopressin and its receptor antagonist on burn shock in the rat.

To investigate the effect of arginine vasopressin (AVP) in the peripheral circulation on burn shock in the rat, AVP and its nonselective V1/V2 receptor antagonist d(CH2)5Tyr (Et)VAVP were administered intravenously in burn shocked rats. Cardiovascular parameters were recorded including left ventricular systolic pressure (LVSP), +/- dP/dt max, total area of the cardiac force loop (Lo), mean arterial blood pressure (MAP), heart rate (HR) and electrocardiogram (ECG). Our results showed that AVP failed to increase MAP in burned rats whereas it elicited a greater fall in LVSP, +/- dP/dt max and Lo and MAP than seen in control burned rats and hastened the onset of the decompensatory phase of burn shock resulting in the early death of burn shocked animals. The receptor antagonist d(CH2)5Tyr(Et)VAVP elevated LVSP, +/- dp/dt max and Lo for the eight hour observation period, and allowed MAP to recover from the initial profound fall following burn injury. Furthermore, it prolonged the survival time of the burned rats. AVP treated rats also displayed earlier abnormal changes such as elevation of S-T segment, inversion of T wave and ventricular fibrillation in ECG. The onset of these changes was much delayed in antagonist treated rats.

Angiotensin Receptor Antagonists↗

Possible involvement of beta-endorphin in the deteriorating effect of arginine vasopressin on burn shock in rats.

The effect of intracerebroventricular injections of arginine vasopressin (AVP) on burn shock in the rat and its possible mechanism were explored in this study. AVP was administered intraventricularly at 30 min intervals (50 ng) in the burned rats. The arterial pressure and electrocardiogram (ECG) were recorded with a multipurpose polygraph before and after burn. Compared with the control, the MAP of the rats in the AVP group was elevated at the initial stage and fell dramatically at the late stage of burn shock with a higher mortality. The ECG of the rats in the AVP group also displayed earlier changes such as elevation of S-T segment, inversion of T wave, and ventricular fibrillation. These findings suggest an unfavorable role of AVP in burn shock. The plasma, hypothalamic, and anterior and posterior pituitary levels of beta-endorphin 3 hr after burn were measured by radioimmunoassay. The increased level of beta-endorphin in the plasma after AVP treatment indicates the possible involvement of beta-endorphin in the deteriorating effect of AVP on burn shock.

Animals↗