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J Sun

Publications and source records attributed to J Sun.

At least 73 records · Page 4Linked to original sources
PubMed2002

Electrolyte transport in the mouse trachea: no evidence for a contribution of luminal K(+) conductance.

Recent studies on frog skin acini have challenged the question whether Cl(-) secretion or Na(+) absorption in the airways is driven by luminal K(+) channels in series to a basolateral K(+) conductance. We examined the possible role of luminal K(+) channels in electrolyte transport in mouse trachea in Ussing-chamber experiments. Tracheas of both normal and CFTR (-/-) mice showed a dominant amiloride-sensitive Na+ absorption under both, control conditions and after cAMP-dependent stimulation. The lumen-negative transepithelial voltage was enhanced after application of IBMX and forskolin and Cl(-) secretion was activated. Electrolyte secretion induced by IBMX and forskolin was inhibited by luminal glibenclamide and the blocker of basolateral Na(+2)Cl(-)K(+) cotransporter azosemide. Similarly, the compound 293B, a blocker of basolateral KCNQ1/KCNE3 K(+) channels effectively blocked Cl(-) secretion when applied to either the luminal or basolateral side of the epithelium. RT-PCR analysis suggested expression of additional K(+) channels in tracheal epithelial cells such as Slo1 and Kir6.2. However, we did not detect any functional evidence for expression of luminal K(+) channels in mouse airways, using luminal 293B, clotrimazole and Ba(2+) or different K(+) channel toxins such as charybdotoxin, apamin and a-dendrotoxin. Thus, the present study demonstrates Cl(-) secretion in mouse airways, which depends on basolateral Na(+2)Cl(-)K(+) cotransport and luminal CFTR and non-CFTR Cl(-) channels. Cl(-) secretion is maintained by the activity of basolateral K(+) channels, while no clear evidence was found for the presence of a luminal K(+) conductance.

Animals↗
PubMed2002

Switch recombination in fetal porcine thymus is uncoupled from somatic mutation.

Since fetal serum Ig isotype profiles suggested that IgG and IgA could be of de novo origin, we studied their transcription and secretion. IgM transcripts were present at 50 days of gestation in major fetal lymphoid tissues, IgG and IgA transcription was pronounced at 60 days in fetal thymus and both transcription and secretion in this organ increased in late fetal life. The CDR3 spectratype of thymic IgG and IgA transcripts was as polyclonal as that of IgM already at 70 days in utero indicating a broad repertoire of switched B-cells. However, VDJs transcribed with the switched isotypes were not hypermutated as were those from immunized fetuses, indicating that switch recombination and somatic mutation are not coupled in utero in piglets. This finding and the fact that the oligoclonal IgA and IgM repertoires in a non-inductive site of the mucosal immune system (parotid gland) becomes polyclonal in piglets reared germ-free, suggest that initial expansion of switched B-cells in fetal and neonatal piglets is not driven by environmental antigen. Our findings collectively suggest that all IgA and IgM may result from de novo synthesis while some IgG probably results from selective transport. The latter is consistent with the gradual decline in serum IgG concentration in germ-free isolator piglets and the expression of FcRn in the porcine placenta.

Animals↗
PubMed2002

Effects of regional hypoxia and acidosis on Rb(+) uptake and energetics in isolated pig hearts: (87)Rb MRI and (31)P MR spectroscopic study.

The study compared the effects of regional hypoxia and acidosis on Rb(+) uptake and energetics in isolated pig hearts perfused by the Langendorff method. The left anterior descending artery (LAD) was cannulated and the LAD bed was perfused with the same specific flow as the whole heart. Following equilibration with normal Krebs-Henseleit buffer (KHB, pO(2) 568 mm Hg, pH 7.42) the perfusate was switched to one that contained Rb(+) (Rb-KHB). Simultaneously, perfusion through the LAD was carried out with hypoxic (pO(2)=31 mm Hg), an acidemic (pH 7.12) or normal (pO(2)=550 mm Hg) Rb-KHB for 120 min. (87)Rb images of the entire heart or localized (31)P spectra from the left ventricular anterior wall were acquired. Hypoxia decreased the maximal (87)Rb image intensity and Rb(+) flux in the anterior wall to 79+/-9% and 85+/-7%, respectively, of that in the posterior wall. Extracellular acidosis did not affect (87)Rb image intensity and reduced Rb(+) flux (83+/-10%). During hypoxia phosphocreatine and ATP decreased to 36+/-10 and 50+/-15% of baseline, respectively and intracellular pH (pHi) decreased to 6.90+/-0.05. Extracellular acidosis did not affect the phosphocreatine or ATP levels but reduced pHi (7.06+/-0.18 vs. 7.26+/-0.06 in control). We suggest that intracellular acidosis plays a role in the inhibition of Rb(+) uptake during hypoxia.

Acidosis↗
PubMed2002

Effect of adrenergic stimulation on Rb(+) uptake in normal and ischemic areas of isolated pig hearts: (87)Rb MRI study.

The role of adrenergic stimulation in Rb(+) uptake in normal and ischemic areas of pig hearts was investigated using an agonist (dobutamine) and an antagonist (S-propranolol). The left anterior descending artery (LAD) in isolated pig hearts was cannulated to maintain adequate perfusion of the LAD bed (2.2-2.8 ml/min/g). Rb(+) loading was initiated by switching perfusion to Rb(+)-containing Krebs-Henseleit (KH) buffer in the presence of 0.1 microM dobutamine, 0.5 microM propranolol, or no drug (control), and the LAD flow was reduced to 10% of the baseline for 120 min. The flow through the LAD was then restored to normal and the drugs were removed. In all groups the rate of Rb(+) uptake obtained from serial (87)Rb images was severely depressed in the ischemic anterior wall relative to that in the normal posterior wall. Dobutamine increased the rate of Rb(+) uptake in the posterior wall (6.3% +/- 1.4% vs. 2.5% +/- 0.25% per minute in control) and did not affect the rate in the anterior wall (0.86% +/- 0.40% vs. 1.14% +/- 0.19% per minute in control). Propranolol did not affect Rb(+) uptake in either of these areas. We conclude that the stimulation of Rb(+) uptake by dobutamine is related to activation of Na(+)/K(+) ATPase and passive Na(+) influx in normal tissue. The lack of any effect of propranolol implies a low level of endogenous norepinephrine during low-flow (LF) ischemia.

Adrenergic beta-Agonists↗
PubMed2002

Cell brain crystallization for cancer therapy.

Cancer remains one of the leading causes of death throughout the world. One of the important reasons why conventional treatments fail is the development of resistance to therapeutics. The dual effect concept and self-defense mechanism plus the threshold theory might in part explain the development of resistance, however, the primary cause is unclear. A novel theory, 'cell brain', where, selective crystallization of the 'brain' of a cell (comprising centrosome, centrioles and the connecting filaments) occurs, may be a potential alternate approach to cancer therapy.

Animals↗
PubMed2002

Stomach cancer-related mortality rate is higher in young Japanese women than in men.

This study compares stomach cancer-related mortality rates in Japan with those in European and Asian countries and analyzes trends in stomach cancer-related mortality rates according to gender in young Japanese over the period of 1957-1997. From official death certification numbers and population estimates, we obtained stomach cancer-related mortality rate for all ages and various ages according to gender. Japan's ranking compared to other countries in death percentage of all cancers which are attributable to stomach cancer was fourth for both men and women. In Japan and Ireland, total elimination of deaths from stomach cancer in men resulted in increased life expectancy of 0.68 and 0.22 y respectively, whereas the corresponding figures for women were 0.42 and 0.14 y respectively. The sex ratios of stomach cancer-related mortality rates were 0.75, 0.63, 0.80 and 0.94 for 25-29, 30-34, 35-39 and 40-44 y age groups, respectively, in 1997. The sex ratio of relative risk ranged from 0.62 to 0.92 in 25-40 y age groups during the observation period. The life expectancy in 30-34 y age group increased by 0.66 y for men and 0.41 y for women in 1995 after elimination of stomach cancer-related deaths. Our results suggest that stomach cancer-related mortality rates are still high in Japan and young women are at higher risk of stomach cancer-related death relative to young men and that sex ratio is stable or slightly decreased over the 40-y period. It is important to monitor this trend continuously in the next few years.

Adult↗
PubMed2002

Bone marrow transplantation for beta-thalassaemia major by an HLA-mismatched parent.

A six-year-old boy was diagnosed with beta-thalassaemia major during infancy. Since then, he required monthly blood transfusion and irregular iron chelation therapy. He had hepatosplenomegaly and elevated liver enzymes; the serum ferritin was up to 3800 ng/mL. An echocardiogram showed left-ventricular enlargement. His one-antigen-mismatched mother was chosen as a bone marrow donor. He was pretreated with intensive red blood cell transfusion and hydroxyurea for 6 weeks prior to conditioning. The conditioning included total body irradiation (300 cGy), busulfan (14 mg/kg), cyclophosphamide (160 mg/kg) and anti-thymocyte globulin (rabbit; 90 mg/kg). Marrow cell dose was 5.4 x 108/kg. Graft versus host disease (GVHD) prophylaxis included cyclosporine A (CSA) and methylprednisolone. Neutrophil engraftment occurred on day 23. Grade II acute GVHD occurred on day 45. The patient developed complications including septicaemia, haemorrhagic cystitis, intracranial haemorrhage and heart failure. He subsequently recovered from the complications without sequelae. The patient remained transfusion-independent at a follow-up examination after 18 months. This case suggested that a mismatched family member may be considered as a bone marrow donor for beta-thalassaemia major. In places where conventional treatment is not feasible, for example, in China, this approach may be an alternative option. A more intensive immunosuppressive regimen and a higher marrow cell dose may be important for successful engraftment. High-dose anti-thymocyte globulin may also prevent severe GVHD.

Bone Marrow Purging↗
PubMed2002

Mortality among Japanese construction workers in Mie Prefecture.

AIMS: A historical cohort mortality study was conducted among 17 668 members of the Construction Workers' Health Insurance Society of Mie Prefecture in Japan, in order to verify the relation between occupations and mortality status. METHODS: The cohort was followed from 2 April 1973 to 1 April 1998. Standardised mortality ratios (SMR) were calculated for all members and each job classification. RESULTS: 98.7% of the members were traced successfully until the date when the follow up terminated. When all members were considered together, significant excess mortality was observed for "accidents and adverse effects". Significant excess mortalities were also observed for lung cancers among scaffold men and ironworkers, for cancer of the oesophagus among plumbers, and for "chronic liver disease and cirrhosis" among scaffold men and painters. CONCLUSION: Results suggest that more detailed investigations, which would include some minor job classifications should be undertaken. This is an updated cohort study which was partially completed in 1997.

Accidents, Occupational↗
PubMed2002

Overexpression of matrix metalloproteinase-8 and -9 in bronchiectatic airways in vivo.

The progressive bronchial dilatation in bronchiectasis is likely to be the result of continued airway matrix destruction, although little is known about the role of neutrophil matrix metalloproteinases (MMPs) in this process. Immunohistochemistry has been used to investigate the expression and cellular localisation of MMP-8 and MMP-9 in bronchiectatic airways in vivo. Endobronchial biopsies were taken from 25 bronchiectatic patients, and from the right lower lobe in 14 control subjects. MMP-8, MMP-9, neutrophils and macrophages were stained with monoclonal antibodies and quantified as positive cell x mm(-2) of the lamina propria by using an image analysis system. There were significantly higher densities of MMP-8 and MMP-9 positive cells in the lamina propria of bronchiectatic than control airways. In bronchiectatic airways, the densities of MMP-8 and MMP-9 positive cells correlated with each other and with neutrophil density, but not with macrophage density. In control airways, a significant correlation was found between MMP-8 with neutrophil and MMP-9 with macrophage densities. An overexpression of neutrophil matrix metalloproteinases in bronchiectatic airways could help explain the continuation of airway destruction in bronchiectasis. In view of the clinical availability of matrix metalloproteinase antagonists, the results presented here could have a significant impact on the development of novel therapies of this untreatable disease.

Aged↗
PubMed2002

Co-removal of hexavalent chromium during copper precipitation.

In our recent study using the nucleated precipitation technology to treat plating wastewater, it was found that about one half of hexavalent chromium was co-removed with copper, nickel and zinc. Since hexavalent chromium could not react with either hydroxide or carbonate to from precipitates, this study was undertaken to evaluate the mechanism(s) involved in the chromium co-removal. Batch tests were conducted with synthetic solutions containing either only copper or both copper and hexavalent chromium. Metal precipitation was induced by adding Na2CO3 to different pH, and the quantitative removal of copper and chromium was determined. Besides, the [Cr]/[Cu] molar ratio of produced precipitates were also assessed in conjunction with the EDAX analysis to determine their compositions. Experimental results indicate that for pure copper solution, precipitation begins at pH 6.0, and completes at pH 7.0. The chemical forms of the precipitates are copper carbonates [CuCO3 x Cu(OH)2 and CuCO3 x 2Cu(OH)2]. On the other hand, in a bi-metal solution of copper plus chromium, precipitation of copper begins at about pH 5.0, and copper precipitation is always accompanied by some chromium removal. From the removal stoichiometry of the two metals, it is found that at low pH, the co-removal is a result of "co-precipitation" which results in the formation of CuCrO4 crystallites. Once such crystallites are formed, they provide a heterogeneous environment which enhances an early formation of copper carbonate at a lower pH (below 5.5). It is further found that once copper carbonate precipitates are produced, the remaining soluble will precipitate in such form, and at this stage further removal of copper is no longer accompanied by additional chromium removal. The test data also reflect that the produced copper carbonates are positively charged, as verified by zeta potential measurement, at pH below 7.5. Thus they are able to adsorb some anionic chromium (existing as chromate) through electrostatic attraction and/or inorganic ligand exchange. At pH of 6 to 10, the extent of adsorption decreases with increasing pH, and the adsorption capacity seems to coincide with the progressive reduction of positive zeta potentials of the precipitated particles.

Adsorption↗
PubMed2001

Estrogen receptor-beta potency-selective ligands: structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues.

Through an effort to develop novel ligands that have subtype selectivity for the estrogen receptors alpha (ERalpha) and beta (ERbeta), we have found that 2,3-bis(4-hydroxyphenyl)propionitrile (DPN) acts as an agonist on both ER subtypes, but has a 70-fold higher relative binding affinity and 170-fold higher relative potency in transcription assays with ERbeta than with ERalpha. To investigate the ERbeta affinity- and potency-selective character of this DPN further, we prepared a series of DPN analogues in which both the ligand core and the aromatic rings were modified by the repositioning of phenolic hydroxy groups and by the addition of alkyl substituents and nitrile groups. We also prepared other series of DPN analogues in which the nitrile functionality was replaced with acetylene groups or polar functions, to mimic the linear geometry or polarity of the nitrile, respectively. To varying degrees, all of the analogues show preferential binding affinity for ERbeta (i.e., they are ERbeta affinity-selective), and many, but not all of them, are also more potent in activating transcription through ERbeta than through ERalpha (i.e., they are ERbeta potency-selective). meso-2,3-Bis(4-hydroxyphenyl)succinonitrile and dl-2,3-bis(4-hydroxyphenyl)succinonitrile are among the highest ERbeta affinity-selective ligands, and they have an ERbeta potency selectivity that is equivalent to that of DPN. The acetylene analogues have higher binding affinities but somewhat lower selectivities than their nitrile counterparts. The polar analogues have lower affinities, and only the fluorinated polar analogues have substantial affinity selectivities. This study suggests that, in this series of ligands, the nitrile functionality is critical to ERbeta selectivity because it provides the optimal combination of linear geometry and polarity. Furthermore, the addition of a second nitrile group beta to the nitrile in DPN or the addition of a methyl substitutent at an ortho position on the beta-aromatic ring increases the affinity and selectivity of these compounds for ERbeta. These ERbeta-selective compounds may prove to be valuable tools in understanding the differences in structure and biological function of ERalpha and ERbeta.

Acetylene↗
PubMed2001

A semi-parametric regression analysis of CD4 cell counts.

This paper considers the regression analysis of CD4 cell counts, a commonly used indicator and prognostic factor of AIDS progression. For this purpose, a number of methods have been proposed and most of them are based on random effects models. We present an alternative that is based on a mean function regression model. The new method is more natural and particularly appropriate if population parameters such as treatment comparison are mainly of interest. To estimate regression parameters, we present an estimating equation-based approach, which does not require estimation of the baseline mean function. This makes the implementation of the approach and the study of the properties of the estimated regression parameters much easier than those based on random effects models. The method is illustrated with a set of CD4 cell count data arising from an AIDS clinical trial and simulated data.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Molecular evolution of catalytic antibodies in autoimmune mice.

Catalytic Abs (catAbs) preferentially evolved in autoimmune MRL/MPJ-lpr/lpr (MRL/lpr) mice upon immunization with the phosphonate transition-state analogue (TSA), but this did not happen in normal BALB/c mice. The majority of the catAbs from MRL/lpr mice were from several independent clones of the same family. Most of them had a lysine at position 95 in the heavy chain (H95), which is at the junctional region. This residue, which interacts with the phosphonate moiety of the TSA and presumably is involved in the catalytic activity, was not changed even after expansive evolution following multiple mutations. By contrast, the majority that arose from BALB/c mice were the non-catAbs, which were quite different in the sequence from the catAbs from MRL/lpr mice, but they were clonally related to one another, so most of them were originated from a single clone. In the MRL/lpr mice, the catalytic subsets that existed in the initial repertoire were effectively captured by the phosphonyl oxygens in the TSA by interacting with the lysine at H95. In the BALB/c mice, however, another noncatalytic subset with only the binding capability directed to a moiety other than the phosphonate moiety was alternatively evolved, because of the lowest abundance or elimination of the catalytic subsets.

Amino Acid Sequence↗
PubMed2001

Synthesis and biological evaluation of a novel series of furans: ligands selective for estrogen receptor alpha.

A variety of nonsteroidal systems can function as ligands for the estrogen receptor (ER), in some cases showing selectivity for one of the two ER subtypes, ER alpha or ER beta. We have prepared a series of heterocycle-based (furans, thiophenes, and pyrroles) ligands for the estrogen receptor and assessed their behavior as ER ligands. An aldehyde enone conjugate addition approach and an enolate alkylation approach were developed to prepare the 1,4-dione systems that were precursors to the trisubstituted and tetrasubstituted systems, respectively. All of the diones were easily converted into the corresponding furans, but formation of the thiophenes and pyrroles from the more highly substituted 1,4-diones was problematical. Of the systems investigated, the tetrasubstituted furans proved to be most interesting. They were ER alpha binding- and potency-selective agents, with the triphenolic 3-alkyl-2,4,5-tris(4-hydroxyphenyl)furans (15a-d) displaying generally higher subtype binding selectivity than the bisphenolic analogues (15f-i). Binding selectivity for ER alpha was as high as 50-70-fold, and transcriptional activation studies showed that several members of this series were ER alpha selective agonists, with the best compound [3-ethyl-2,4,5-tris(4-hydroxyphenyl)furan, 15b] having full transcriptional activity on ER alpha while being inactive on ER beta. Comparative binding affinity analysis and molecular modeling were used to investigate the preferred binding mode adopted by the furan ligands, which appears to have the C(2) phenol mimicking the important role of the A-ring of estradiol. These ligands should be useful in studying the biological roles of both ER alpha and ER beta, and they might form the basis for the development of novel estrogen pharmaceuticals.

Animals↗
PubMed2001

The cell type-specific expression of the murine IL-13 gene is regulated by GATA-3.

IL-13, a Th2 cell-specific cytokine, is a major effector molecule mediating several pathological features of allergic asthma. However, the transcriptional regulation of the IL-13 gene remains unclear. Here we demonstrate, by using intracellular cytokine staining, that IL-13 is not always coexpressed with other Th2 cytokines in normal Th cells on a single cell basis. In addition, we identified and cloned a minimal inducible and cell type-specific promoter of the murine IL-13 gene. The cell type specificity of the minimal IL-13 promoter is mediated by a functionally critical GATA-3 site that binds endogenous GATA-3 proteins, whereas the induction by PMA/ionomycin is mediated by distinct cis-acting elements. Furthermore, by expressing GATA-3 in wild-type and c-maf transgenic Th1 cells, we demonstrate that the expression of IL-13 is regulated by a mechanism distinct from that regulating the expression of IL-4, and that the expression of Th1 and Th2 cytokine genes does not have to be mutually exclusive in effector Th cells.

Animals↗
PubMed2001

A recombinant glycine receptor fragment forms homo-oligomers distinct from its GABA(A) counterpart.

The ligand-gated ion channel receptor superfamily includes receptors for glycine, GABA, acetylcholine and serotonin. Whereas the acetylcholine and serotonin receptors mediate excitory neurotransmissions, both glycine and GABA(A) receptors are inhibitory. In this study, a fragment of the human glycine receptor alpha1 subunit, consisting of residues Ala165-Met291 (numbering based on the precursor protein), was hyperexpressed for the first time in Escherichia coli. This fragment is highly homologous in sequence to the corresponding fragment of the GABA(A) receptor. The recombinant fragment was found to have stable beta-rich secondary structure, similar to that found for the homologous GABA(A) receptor fragment, and ordered tertiary packing, suggesting a stable structural domain. Results from laser scattering studies suggest that the fragment forms trimers in solution. In addition, SDS-induced changes in secondary structure were found to occur prior to changes in oligomerization status, suggesting that oligomerization was secondary structure dependent. A study of quaternary structure using single particle analysis electron microscopy (EM) also suggested that the fragment formed homo-trimers. One trimer measures approximately 7.5 nm in diameter with a central cavity approximately 1.5 nm across. This is the first EM study on a single domain of the glycine receptor and the result is in contrast to the pentameric assembly of the equivalent GABA(A) receptor fragment reported by us earlier. The fact that this fragment alone could form oligomers in vitro suggests that amino acid residues within this segment may be involved in the oligomerization of the glycine receptor in vivo. Furthermore, the finding that two cousin receptor fragments form distinct quaternary structures indicates that sequence similarity does not necessarily imply quaternary structure similarity and, hence, care must be taken when applying a structure model derived from studies of individual receptors to the whole ligand-gated ion channel superfamily.

Amino Acid Sequence↗
PubMed2001

Sensitization of differentiated PC12 cells to apoptosis by presenilin-2 is mediated by p38.

Presenilin 2 (PS2), the chromosome 1 familial Alzheimer's disease gene, has been shown to sensitize differentiated PC12 (dPC12) cells to apoptosis. In this investigation we show that activation of the p38 mitogen activated protein kinase pathway occurs downstream of PS2 and is required for sensitizing the cells to apoptosis. Overexpression of PS2 led to a dramatic increase in p38 activity, which is correlated with an increased susceptibility of dPC12 cells to apoptosis. Inhibition of p38 by the specific inhibitor SB203580 or interfering with the p38 pathway by overexpression of dominant negative MKK6 effectively blocked PS2 sensitized apoptosis. Expression of ALG-3, a truncated PS2 which acts as a dominant negative PS2, significantly suppressed p38 activation induced by trophic factor withdrawal. These data suggest that PS2 is a signaling molecule upstream of the p38 MAPK pathway in apoptotic dPC12 cells.

Animals↗