Biomedical subjects

J Sun

Publications and source records attributed to J Sun.

At least 127 records · Page 7Linked to original sources

PubMed2001

v-Src transformation is mediated through farnesylated proteins.

Src is an oncoprotein which has been implicated in a number of human malignancies in which it has been shown to be overexpressed and highly activated. The precise mechanism of Src transformation, however, is still poorly understood. We hypothesized that Ras and other farnesylated proteins may mediate Src transformation. To test this hypothesis, v-Src-transfected rat fibroblasts (3Y1) were treated every 72 h with a 15 microM concentration of a farnesyl-transferase inhibitor (FTI). At 2 weeks, a focus formation assay was performed to assess transformation potential. Untreated and FTI-treated v-Src-transfected 3Y1 cells formed a mean of 39 (+/-2.6) and 29.8 (+/-2.9) foci per well, respectively. This 24% decrease was judged to be statistically significant (P = 0.02). Moreover, foci (>90%) in the FTI-treated wells were also consistently smaller than foci in the untreated wells. Western blots with antibody directed toward H-Ras confirmed complete inhibition of Ras farnesylation in the treated cell lines. The specificity of this inhibition was verified by Western blot using antibody specific for Rap1A. The transforming potential of v-Src is inhibited, but not eliminated by FTI treatment. This suggests that v-Src transformation is mediated in part by farnesylated proteins, one of which may be Ras.

Alkyl and Aryl Transferases↗

PubMed2001

Derivative hydride generation atomic absorption spectrometry and determination of lead traces in waters.

Fundamentals of derivative hydride-generation atomic absorption spectrometry (DHGAAS) are described. A linear relationship was obtained between the derivative absorbance and the concentration of analysis in a sample. The new DHGAAS method was applied to the determination of traces of lead in water. The conditions affecting the derivative absorbance of lead were evaluated and optimized. The detection limit and sensitivity of the proposed method were 26 times and 8.8 times better, respectively, than those of conventional hydride-genera-tion atomic absorption spectrometry. The characteristic concentration (for a derivative absorbance of 0.0044) and detection limit (3sigma) for lead were 0.017 and 0.096 ng mL(-1), respectively, for a 2 mV min(-1) sensitivity range setting. The recovery range was 92.5-103%.

Acids↗

PubMed2001

Flocculation and coflocculation of bacteria by yeasts.

Biotransformations in natural environments frequently involve interactions between microorganisms. Although there are many reports on the interactions between bacteria, interactions between yeasts and bacteria have not been extensively studied. Previously we reported on the flocculation and coflocculation of Pediococcus damnosus by Saccharomyces cerevisiae. Now we report that several other yeasts, such as Candida utilis, Dekkera bruxellensis, Hanseniaspora guilliermondii, Kloeckera apiculata, and Schizosaccharomyces pombe, induce flocculation with several industrially or medically relevant bacteria, including Bacillus subtilis, Pseudomonas aeruginosa, and Staphylococcus aureus. Candida utilis was one of the best flocculation inducers. The results are discussed with respect to interactions between yeasts and bacteria and their applications in industry and medicine.

Bacillus subtilis↗

PubMed2001

Coflocculation of Escherichia coli and Schizosaccharomyces pombe.

Several yeasts, such as Candida utilis, Dekkera bruxellensis, Hanseniaspora guilliermondii, Kloeckera apiculata, Saccharomyces cerevisiae and Schizosaccharomyces pombe, were found to coaggregate with Escherichia coli, but S. pombe showed much less coflocculation than the other yeasts (Peng et al. 2001)). S. pombe is known to have galactose-rich cell walls and we investigated whether this might be responsible for its different behavior by studying the wild-type TP4-1D, with a mannose to galactose ratio of 1 to 1.2, and the glycosylation mutant gms1delta (Man:Gal=1:0). The wild-type induced very low levels of coflocculation (3%) while gms1delta induced a remarkable amount of coflocculation (48%). Coflocculation of the mutant was inhibited by mannose but not affected by galactose or glucose. The S. cerevisiae mnn2 mutant, with a mannan structure similar to gms1delta, also showed a high degree of coflocculation (40%). However, S. cerevisiae mutant mnn9, with a mature core similar to S. pombe, showed decreased coflocculation (21.3%). Both these S. cerevisae mutants were sensitive to mannose inhibition. Coflocculation of E. coli and gms1delta also could be inhibited by gms1delta mannan and plant lectins, such as HHA, GNA and NPA, specific to either alpha-1-3- or alpha-1-6-linked mannosyl units. From these results we conclude that the E. coli lectins may have specificity for alpha-1-6- and alpha-1-3-linked mannose residues either in the outer chain or in the core of S. pombe, but in wild-type strains these mannose residues are shielded by galactose residues.

Carbohydrate Sequence↗

PubMed2001

Cgr1p, a novel nucleolar protein encoded by Saccharomyces cerevisiae orf YGL0292w.

Saccharomyces cerevisiae open reading frame (ORF) YGL029w (CGR1) encodes a small hydrophilic protein of unknown function. To investigate the role of this gene, we have determined the intracellular localization of the encoded product and examined the effects of Cgr1p depletion on cell growth. Tagging Cgr1p with the green fluorescent protein (GFP) or the myc epitope showed focal accumulation of the fusion protein in the yeast nucleolus, and this localization overlapped with the distribution of the nucleolar protein Nop1p. Cells depleted of CGR1 mRNA were growth impaired and hypersensitive to the translational inhibitor paromomycin, and this phenotype was complemented by episomal expression of the CGR1-GFP fusion gene. These results identify Cgr1p as a novel component of the yeast nucleolus and suggest a potential role in ribosome biogenesis.

Fungal Proteins↗

PubMed2001

Molecular cloning of cgrA, the gene encoding the Aspergillus nidulans ortholog of Saccharomyces cerevisiae CGR1.

Saccharomyces cerevisiae CGR1 encodes a 120-amino acid protein with a predominant nucleolar localization. In this study we report the identification and cloning of the ortholog, cgrA, from Aspergillus nidulans. The cgrA gene is comprised of three exons on A. nidulans Chromosome 7. The cDNA contains a single open reading frame (ORF) that would encode a protein of 114 amino acids with 44% sequence identity to yeast Cgr1p. A plasmid expressing cgrA complemented the impaired growth phenotype of a yeast strain that can be inducibly depleted of CGR1, and a green fluorescent protein (GFP)-tagged CgrA protein had the same nucleolar localization as the corresponding yeast protein. These results identify cgrA as the A. nidulans ortholog of yeast CGR1 and suggest evolutionary conservation of nucleolar localization mechanisms used by these proteins.

Amino Acid Sequence↗

PubMed2001

The role of internal reflection in transskull phase distortion.

Phase distortion due to reflection in transcranial ultrasound propagation is investigated. Understanding of these phase-dependent properties is motivated by efforts to construct a reliable prediction model for noninvasive ultrasound therapy in the brain. The present study measures the phase of an ultrasound wave after propagation through an ex vivo human skull and considers the dependence of this phase on reflections between the transducer and the skull surface in addition to reflections within the skull. Experiments are performed using a human calvarium fragment placed between an underwater ultrasonic transducer and a polyvinylidene difluoride hydrophone. Data are presented indicating the ultrasound phase dependence as a function of burst length and the distance of the transducer element from the skull at a driving frequency of 0.5 MHz. Experimental results are compared with predictions obtained from a propagation model which considers transmission at the skull interfaces as well as multiple reflections within the skull. It is concluded that by using short ultrasound bursts a distance may be indicated that beyond which the contributions of transducer reflections on the phase of the propagating wave may be neglected. Additionally, a comparison of the measurements with simulated data supports the contention that for reasonably small incident angles, reflection within the skull causes minimal phase shift.

Brain↗

PubMed2001

Glutamate induced modulation of free Ca(2+) in isolated inner hair cells of the guinea pig cochlea.

To explore the possible involvement of glutamate (Glu) in modulation of inner hair cell (IHC) functions, the glutamate (Glu) induced changes in intracellular free Ca(2+) ([Ca(2+)]i) concentration in isolated IHCs and outer hair cells (OHCs) of the guinea pig cochlea were investigated with fluo-3, a fluorescent probe for intracellular Ca(2+). Their unique flask shape identified the IHCs with a distinct neck and spherical base with a large spherical nucleus. Normal cell shapes could be maintained for about 2 h. Fluorescence of fluo-3 was distributed in the whole isolated IHC with brighter staining nuclei. Static [Ca(2+)]i remained constant within the observation period in the absence of Glu. In the presence of a low concentration of Glu (3.85 microM), there was an increase of [Ca(2+)]i in IHCs, whereas no obvious [Ca(2+)]i change was found in OHCs. The increase of the fluorescence in IHCs reached peak level at 180 s and then gradually reduced at 400 s after the administration of Glu. The increases of [Ca(2+)]i were observed in nine of 10 IHCs, but one IHC did not show any change. For 10 of the observed OHCs, seven showed no [Ca(2+)]i change, and three showed minor reduction of [Ca(2+)]i. The increase of the Glu concentration resulted in a corresponding change of [Ca(2+)]i in the IHCs after three times administration of Glu. These results suggest that Glu acts on the IHCs presynaptic autoreceptor in a positive feedback manner.

Animals↗

PubMed2001

Is deep hypothermia necessary for unilateral antegrade cerebral perfusion during circulatory arrest? A magnetic resonance study in a pig model.

OBJECTIVE: Localized (31)P magnetic resonance spectroscopy (MRS) was used to investigate whether unilateral antegrade cerebral perfusion (U-ACP) could maintain normal energy metabolism and intracellular pH (pHi) in both hemispheres of the brain during deep (15 degrees C) and moderate (28 degrees C) hypothermic circulatory arrest (HCA). METHODS: Eleven pigs were exposed to 120 min of U-ACP during HCA at 15 degrees C (group I, n=6) or 28 degrees C (group II, n=5), followed by 60 min of cardiopulmonary bypass (CPB) at 37 degrees C. Localized (31)P MR spectra were acquired every 30 min. Histopathology was performed at the completion of each experiment. RESULTS: MR recorded no changes in energy metabolites (phosphocreatine and ATP), or pHi during U-ACP in either group, and no significant differences were found in any of the energy metabolites or pHi between the left and right hemispheres. Histopathology showed no significant morphological changes in the neurons. CONCLUSIONS: During either deep or moderate HCA, unilateral ACP through the right axillary artery prevents ischemic events in both hemispheres of normal pig brains. Deep hypothermia may not be necessary when using U-ACP.

Animals↗

PubMed2001

Triarylpyrazoles with basic side chains: development of pyrazole-based estrogen receptor antagonists.

Recently, we developed a novel triaryl-substituted pyrazole ligand system that has high affinity for the estrogen receptor (ER) (Fink, B. E.: Mortenson, D. S.: Stauffer, S. R.; Aron, Z. D.: Katzenellenbogen, J. A. Chem. Biol. 1999, 6, 205). Subsequent work has shown that some analogues in this series are very selective for the ERalpha subtype in terms of binding affinity and agonist potency (Stauffer, S. R.: Coletta, C. J.: Tedesco. R.: Sun, J.: Katzenellenbogen, J. A. J. Med. Chem. 2000, submitted). We now investigate how this pyrazole ER agonist system might be converted into an antagonist or a selective estrogen receptor modifier (SERM) by incorporating a basic or polar side chain like those typically found in antiestrogens and known to be essential determinants of their mixed agonist/antagonist character. We selected an N-piperidinyl-ethyl chain as a first attempt, and introduced it at the four possible sites of substitution on the pyrazole core structure to determine the orientation that the pyrazole might adopt in the ER ligand binding pocket. Of these four, the C(5) piperidinyl-ethoxy-substituted pyrazole 5 had by far the highest affinity. Also, it bound to the ER subtype alpha (ERalpha) with 20-fold higher affinity than to ERbeta. In cell-based transcription assays, pyrazole 5 was an antagonist on both ERalpha and ERbeta, and it was also more potent on ERalpha. Based on structure-binding affinity relationships and on molecular modeling studies of these pyrazoles in a crystal structure of the ERalpha-raloxifene complex, we propose that pyrazoles having a basic substituent on the C(5) phenyl group adopt a binding mode that is different from that of the pyrazole agonists that lack this group. The most favorable orientation appears to be one which places the N(1) phenol in the A-ring binding pocket so that the basic side chain can adopt an orientation similar to that of the basic side chain of raloxifene.

Binding Sites↗

PubMed2001

Nonparametric test for doubly interval-censored failure time data.

This paper considers comparison of discrete failure time distributions when the survival time of interest measures elapsed time between two related events and observations on the occurrences of both events could be interval-censored. This kind of data is often referred to as doubly interval-censored failure time data. If the occurrence of the first event defining the survival time can be exactly observed, the data are usually referred to as interval-censored data. For the comparison problem based on interval-censored failure time data, Sun (1996) proposed a nonparametric test procedure. In this paper we generalize the procedure given in Sun (1996) to doubly interval-censored data case and the generalized test is evaluated by simulations.

Cohort Studies↗

PubMed2001

Respiratory ciliary function in bone marrow recipients.

Bone marrow transplantation (BMT) recipients, particularly those with chronic graft-versus-host disease (GVHD), suffer from respiratory tract problems, including bronchiolitis obliterans (BO) and recurrent lower respiratory tract infections. Minute cilia beat continuously on the surface of respiratory mucosa, and this beating maintains the sterility of the lower respiratory tract. Dysfunction of respiratory cilia could lead to development of recurrent respiratory tract infections, which are also features of BMT recipients, although ciliary function has not been systematically studied among these subjects. We have, therefore, investigated the ciliary beat frequency (CBF) of 36 Chinese patients who had undergone allogeneic BMT. The CBF was significantly lower in the BMT group compared to controls (P < 0.001). The reduction in CBF was more severe in patients with cGVHD and BO compared with their counterparts (P = 0.048 and P = 0.077, respectively). There was a correlation between CBF with forced expiratory flow rate FEF (P = 0.024) and forced expiratory volume FEV (P = 0.044). We conclude that abnormal ciliary clearance is a common feature after allogeneic BMT, particularly among patients with BO and cGVHD. Further studies are indicated to evaluate this important phenomenon, which could be an important cause of the susceptibility for BMT recipients to respiratory infections.

Adolescent↗

PubMed2001

Induction of ppGpp synthesis in Streptomyces coelicolor A3(2) grown under conditions of nutritional sufficiency elicits actII-ORF4 transcription and actinorhodin biosynthesis.

Production of ppGpp in Streptomyces coelicolor A3(2) was achieved independently of amino acid limitation by placing N-terminal segments of the ppGpp synthetase gene, relA, under the control of a thiostrepton-inducible promoter (tipAp). S1 nuclease protection experiments indicated that induced ppGpp concentrations of 6-12 pmol mg(-1) dry weight in late-exponential phase cultures caused activation of transcription of actII-ORF4, the pathway-specific activator gene for actinorhodin production. This level of ppGpp had no effect on growth rate, implying a causal role for ppGpp in activating actII-ORF4 transcription. No effect was observed on the transcription of the corresponding and homologous activator gene for undecylprodigiosin production, redD, reflecting a requirement for additional regulatory factors for activation of its transcription. This work provides the most compelling evidence yet for the activation of an antibiotic biosynthetic pathway by the stringent factor ppGpp.

Alcohol Oxidoreductases↗

PubMed2001

Globalization of tertiary nursing education in post-Mao China: a preliminary qualitative assessment.

This article examines China's collaborative initiatives with Western countries to assess the impact of globalization on Chinese nursing education, especially at the post-secondary level, in the post-Mao era. Through the theoretical framework of mutuality, it evaluates the outcomes of globalization in two broad domains: pedagogy and system-institution-program building. In addition, case studies on two collaborative projects between Chinese nursing programs and Western institutions were conducted to further illustrate the principles of mutuality. This qualitative assessment is primarily based on a systematic review of published studies on the multifaceted dimensions of globalization in Chinese post-secondary nursing education in both English and Chinese nursing literature since 1990. It is supplemented by unpublished documents and data obtained from a research trip to China in 2000. The study concludes that globalization has been, and will remain, one of the major forces underpinning Chinese nursing education (and the nursing profession in general), which is moving towards integration into the global nursing community. However, there is a significant imbalance in the knowledge transfer equation both in the national and international context. Great efforts need to be made to synthesize nursing knowledge in the East and West to achieve an integrative nursing science.

Canada↗

PubMed2001

Baccalaureate nursing education curricula in the People's Republic of China: status, issues and reforms.

This article examines baccalaureate nursing education curricula in the People's Republic of China. Three 5-year curricula and one 4-year curriculum were content analyzed and contrasted. Findings of this study suggested that: (i) the biomedical model dominated the three 5-year traditional curricula; (ii) political-ideological content permeated all four curricula; and (iii) the reformed curriculum at Peking Union Medical College was a genuine effort toward building a new nursing curriculum model that intended to differentiate nursing education from medical education. In addition, major themes of recent curriculum reforms were highlighted. Recommendations were suggested to improve the outcomes of future curriculum endeavors. Explicit as well as implicit comparisons with an ideal-typical American generic baccalaureate nursing curriculum were made when appropriate.

China↗

PubMed2001

Prevalence of naturally occurring surface gene variants of hepatitis B virus in nonimmunized surface antigen-negative Chinese carriers.

Previous studies have suggested that hepatitis B virus (HBV) variants may account for the presence of HBV DNA in hepatitis B surface antigen (HBsAg)-negative patients (occult HBV infection). However, it is not known how widespread these variants are and how they influence the course of liver disease. To determine the prevalence of variants within the major hydrophilic region (MHR) of HBsAg, we investigated 2,565 subjects, including subjects with chronic hepatitis, cryptogenic cirrhosis, hemodialysis patients, and blood donors. Fifty-one of them had occult HBV infection. The entire S gene from 46 of these patients was sequenced from amplified serum HBV DNA. Forty-three percent (20 of 46) had mutations in the MHR of HBsAg. Thirty-two amino acid substitutions between positions 100-160 of the MHR of HBsAg were detected in 18 patients, and these ranged from 1 to 4 per patient. These changes involved 11 positions inside and 5 outside of the historical first and second loops of the "a" determinant, and included the following: Q101K, T115A, K122N, T123A, T126N, Q129N, G130R, T131I, M133T, F134L, C138Y, K141E, P142S, G145R, N146S, and C147F/R. Combinations of mutations were detected in 9 patients, and 7 of these have not been described before. Two further patients had insertion mutations immediately before the "a" determinant. Monoclonal antibody binding tests with the Royal Free hepatitis B surface (RFHBs) panel of antibodies revealed decreased immunoreactivity in 6 novel variants of HBsAg. The existence of patients with occult HBV infection caused by HBsAg variants, therefore, has implications for their possible transmission through sexual contact and by blood transfusion.

Alanine Transaminase↗

PubMed2001

Effect on myocardial perfusion of simultaneous delivery of cardioplegic solution through a single coronary artery and the coronary sinus.

OBJECTIVE: This study was to determine whether simultaneous antegrade-retrograde cardioplegia through a single coronary artery and the coronary sinus provides sufficient and homogeneous perfusion to the heart. METHODS: Simultaneous antegrade-retrograde cardioplegia was conducted in 7 isolated pig hearts through the coronary sinus in conjunction with the left anterior descending artery, the left circumflex artery, and the right coronary artery, respectively. The efficacy of simultaneous antegrade-retrograde cardioplegia for myocardial perfusion was assessed by monitoring the distribution of magnetic resonance contrast agent and measuring the effluent from the venting coronary arteries. RESULTS: Injection of contrast agent into a perfusing artery during simultaneous antegrade-retrograde cardioplegia resulted in increased image signal intensity not only in the territory of the perfusing artery but also in the areas normally served by the other 2 venting arteries (including the right ventricular wall). The myocardium in the territories of the 2 venting arteries was lightened with contrast agent given into the coronary sinus during simultaneous antegrade-retrograde cardioplegia. Myocardium in the perfusing artery territory and right ventricular wall remained dark. Moreover, a significant amount of effluent was collected from the venting arteries during simultaneous antegrade-retrograde cardioplegia: 4.7 to 7.8 mL/min from the right coronary artery; 10.5 to 17.7 mL/min from the left anterior descending artery; and 9.7 to 15.2 mL/min from the left circumflex coronary artery. CONCLUSIONS: Simultaneous antegrade-retrograde cardioplegia through a single coronary artery and the coronary sinus provides homogeneous perfusion to the entire heart. During simultaneous antegrade-retrograde cardioplegia, arterial flow supports its own designated myocardium, as well as adjacent myocardium normally served by the venting arteries; the arterial route also supports the right ventricular free wall when the right coronary artery is vented. Venous perfusion of simultaneous antegrade-retrograde cardioplegia mainly supports myocardium in the territories of the venting arteries and does not perfuse the right ventricular free wall. Blood flow delivered to myocardium normally supported by the venting arteries is believed to be sufficient to prevent ischemic injury.

Animals↗

PubMed2001

Contrast agent distribution in microvascular damage of infarcted pig myocardium.

PURPOSE: We determined whether reperfusion damage was sufficient to allow extravasation of a large molecular weight contrast agent into infarcted pig myocardium. MATERIAL AND METHODS: Five pig hearts were subjected to in situ occlusion of the left anterior descending coronary artery (2 h) followed by reperfusion (1 h). The hearts were excised and perfused in the Langendorff mode for ex vivo MR imaging. Polylysine-Gd-DTPA (50,000 Da) and Gd-DTPA (500-700 Da) were injected into the aorta (alternately) and followed by measurements of T1 relaxation and mean transit time (MTT). RESULTS: In the normal myocardium, MTT of Gd-DTPA (56.8+/-23.2 s) was significantly (p=0.02) longer than that of polylysine-Gd-DTPA (29.0+/-7 s). However, both normal and infarcted myocardium showed similar MTT (29.0+/-7.0 vs. 28.0+/-5.0 s, p>0.05) when using polylysine-Gd-DTPA. CONCLUSION: The results indicate that the permeability of capillaries to polylysine-Gd-DTPA was not significantly higher in infarcted regions of the myocardium compared to normal tissue. However, infarcted myocardium displayed an increased permeability to the small molecular weight Gd-DTPA. We conclude that microvascular damage may not be sufficient to allow the extravasation of polylysine-Gd-DTPA in infarcted myocardium.

Animals↗