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Biomedical subjects

Z Sun

Publications and source records attributed to Z Sun.

At least 253 records · Page 14Linked to original sources

In vitro reaction of macrophages to metal ions from dental biomaterials.

OBJECTIVES: This study was conducted to 1) measure the sensitivity of human and mouse macrophages to metal ions which are released from dental biomaterials, 2) compare these sensitivities with those of other cell types in the oral cavity, and 3) determine if metal ions alter the metabolism and synthetic processes of these cells at lower concentrations than are required to lyse the cells. This information will help define the biological risks associated with the release of metal ions into the oral cavity. METHODS: Macrophages were exposed to a range of concentrations of Ag1+, Au3+, Cu2+, Hg2+, Ni2+, Pd2+, Pt4+, and Zn2+ for 24 h in cell culture. The concentrations which caused a 50% decrease in succinic dehydrogenase (SDH) activity, protein production, and lactate dehydrogenase (LDH) release were measured and compared with these values for fibroblasts and osteoblasts. RESULTS: Most metal ions caused alteration in SDH activity and protein production at lower concentrations than were required to induce LDH release. There were exceptions to this trend, and the differences were not always statistically significant. Furthermore, although the macrophages sometimes had statistically different sensitivities to metal ions than fibroblasts or osteoblasts, these differences were less than one order of magnitude. Macrophage response to the metal ions was highly dependent on the metal ion and the species of macrophage. SIGNIFICANCE: Macrophages react adversely to metal ions at similar concentrations as other cell types found in the oral cavity. Furthermore, the concentrations which affect cell metabolism and protein production are generally lower than those which lyse the cells. Thus, non-lethal concentrations of metal ions may alter the secretion of protein inflammatory mediators such as cytokines which direct the inflammatory response in tissues.

Analysis of Variance↗

Postinfarction ventricular septal rupture: repair by endocardial patch with infarct exclusion.

A novel operative technique for postinfarction ventricular septal defect has been used in 44 consecutive patients. The operation consists of excluding rather than excising the infarcted septum and ventricular walls. This is accomplished by performance of a left ventriculotomy through the infarcted muscle and securing a glutaraldehyde-fixed bovine pericardium patch to the endocardium of the left ventricle all around the infarcted myocardium. The ventriculotomy is simply closed over the pericardial patch. There were 21 men and 23 women whose mean age was 69 +/- 7 years. Twenty-nine patients were in cardiogenic shock at the time of operation. All patients had Doppler echocardiography and coronary angiography before operation. All but two patients were operated on during the acute phase of the myocardial infarction. There were six operative deaths. Postoperative complications included renal failure in 10 patients and respiratory failure in 18. Severe right ventricular dysfunction was the only independent predictor of operative mortality. Patients have been followed up for a mean of 40 +/- 34 months. There have been six late deaths and three of these were because of cardiac problems. The actuarial survival at 6 years was 66% +/- 7%. Only one patient had a small residual ventricular septal defect. Late postoperative assessment of ventricular function by echocardiography revealed that most patients had normal or mild impairment of right ventricular function and mild or moderate impairment of left ventricular function. Repair of acute postinfarction ventricular septal defect by endocardial patch with infarct exclusion of the left ventricule probably avoids additional damage to the right ventricle, remodels the acutely infarcted left ventricle, and enhances survival.

Aged↗

Reconstruction of the mitral anulus. A ten-year experience.

Reconstruction of the mitral anulus was done in 93 patients because of extensive calcification in 24, infective endocarditis with annular abscess in 27, damaged anulus as a result of previous valve replacement in 36, and rupture of the posterior wall of the left ventricle after mitral valve replacement in 6. The reconstruction was done with fresh autologous pericardium in 30 patients, glutaraldehyde-fixed bovine pericardium in 56, and Dacron graft in 7. An appropriately tailored patch was sutured to the endocardium of the left ventricle or to fibrous skeleton of the heart, or to both. Sixty patients had had previous operation; most patients were in New York Heart Association functional class IV and 15 were in shock. The mitral valve was repaired in 10 patients and replaced in 83. Other procedures were aortic valve replacement in 40, tricuspid valve repair in 25, coronary artery bypass in 12, and replacement of the ascending aorta in 2. Eight patients died in the perioperative period. Postoperative complications were common. Patients were followed up from 12 to 96 months, with a mean of 30 months. There have been 18 late deaths, mostly cardiac. The actuarial survival at 5 years was 68% +/- 6%. A total of 8 patients have required reoperation: 4 because of endocarditis, 2 because of bioprosthetic valve failure, and 2 because of patch dehiscence. The freedom from reoperation was 80% +/- 8% at 5 years. The freedom from patch dehiscence was 95% +/- 4% at 5 years. Reconstruction of the mitral anulus has been an extremely useful operative technique for patients with complex mitral valve disease.

Adolescent↗

Calspermin gene transcription is regulated by two cyclic AMP response elements contained in an alternative promoter in the calmodulin kinase IV gene.

The transcript for the high-affinity Ca2+/calmodulin-binding protein calspermin is generated from the gene encoding Ca2+/calmodulin-dependent protein kinase IV only in postmeiotic germ cells during spermatogenesis. We demonstrate that this testis-specific calspermin transcript can be produced in heterologous cells by utilization of a promoter located in an intron of the calmodulin (CaM) kinase IV gene. Critical motifs within this promoter are two cyclic AMP response element (CRE)-like sequences located about -70 and -50 bp upstream of the transcriptional initiation site. Both CRE motifs are footprinted by the authentic testis-specific transcriptional activator CREM tau or by CREM tau present in adult testis nuclear extract. Whereas a 2.1-kb DNA fragment containing the calspermin promoter is inactive when transfected into NIH 3T3 cells, activity can be restored by cotransfection of CREM tau and protein kinase A or CaM kinase IV but not CaM kinase II alpha. Restoration of activity is greatly reduced by mutation of the two CRE motifs. Since CRE-like motifs have been identified in many genes uniquely expressed in postmeiotic germ cells, which contain abundant CREM tau protein, we suggest that CREM tau may function as one transcription factor responsible for the expression of postmeiotic germ cell-specific genes.

3T3 Cells↗

PU.1 (Spi-1) and C/EBP alpha regulate expression of the granulocyte-macrophage colony-stimulating factor receptor alpha gene.

Growth factor receptors play an important role in hematopoiesis. In order to further understand the mechanisms directing the expression of these key regulators of hematopoiesis, we initiated a study investigating the transcription factors activating the expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha gene. Here, we demonstrate that the human GM-CSF receptor alpha promoter directs reporter gene activity in a tissue-specific fashion in myelomonocytic cells, which correlates with its expression pattern as analyzed by reverse transcription PCR. The GM-CSF receptor alpha promoter contains an important functional site between positions -53 and -41 as identified by deletion analysis of reporter constructs. We show that the myeloid and B cell transcription factor PU.1 binds specifically to this site. Furthermore, we demonstrate that a CCAAT site located upstream of the PU.1 site between positions -70 and -54 is involved in positive-negative regulation of the GM-CSF receptor alpha promoter activity. C/EBP alpha is the major CCAAT/enhancer-binding protein (C/EBP) form binding to this site in nuclear extracts of U937 cells. Point mutations of either the PU.1 site or the C/EBP site that abolish the binding of the respective factors result in a significant decrease of GM-CSF receptor alpha promoter activity in myelomonocytic cells only. Furthermore, we demonstrate that in myeloid and B cell extracts, PU.1 forms a novel, specific, more slowly migrating complex (PU-SF) when binding the GM-CSF receptor alpha promoter PU.1 site. This is the first demonstration of a specific interaction with PU.1 on a myeloid PU.1 binding site. The novel complex is distinct from that described previously as binding to B cell enhancer sites and can be formed by addition of PU.1 to extracts from certain nonmyeloid cell types which do not express PU.1, including T cells and epithelial cells, but not from erythroid cells. Furthermore, we demonstrate that the PU-SF complex binds to PU.1 sites found on a number of myeloid promoters, and its formation requires an intact PU.1 site adjacent to a single-stranded region. Expression of PU.1 in nonmyeloid cells can activate the GM-CSF receptor alpha promoter. Deletion of the amino-terminal region of PU.1 results in a failure to form the PU-SF complex and in a concomitant loss of transactivation, suggesting that formation of the PU-SF complex is of functional importance for the activity of the GM-CSF receptor alpha promoter. Finally, we demonstrate that C/EBP alpha can also active the GM-CSF receptor alpha promoter in nonmyeloid cells. These results suggest that PU.1 and C/EBP alpha direct the cell-type-specific expression of GM-CSF receptor alpha, further establish the role of PU.1 as a key regulator of hematopoiesis, and point to C/EBP alpha as an additional important factor in this process.

Amino Acid Sequence↗

Effect of renal denervation on elevation of blood pressure in cold-exposed rats.

The objective of this experiment was to determine whether bilateral renal denervation (RD) prevents the elevation of blood pressure and cardiac hypertrophy characteristically induced by chronic exposure to cold. Four groups (nine male rats each) were used. The kidneys of two groups were bilaterally denervated, while the remaining two groups were sham operated. Systolic blood pressures of the four groups, measured indirectly from the tail, did not differ significantly during the control period and following RD. At this time, 1 RD and 1 sham-operated group was exposed to cold (5 degrees C, 41 degrees F). The remaining RD and sham-operated groups were kept at 25 degrees C. Blood pressure of the cold-exposed, sham-operated group increased significantly during the 1st week of cold exposure (125 +/- 2 mmHg; 1 mmHg = 133.3 Pa), and rose to 139 +/- 4 mmHg by the 5th week, whereas the blood pressure of the RD group exposed to cold remained at the control level (116 +/- 2 mmHg). Both RD and sham-operated cold-exposed groups developed cardiac hypertrophy with significantly increased resting heart rates compared with controls kept at 25 degrees C. Plasma renin activities and renal norepinephrine content of kidneys of both RD groups at 7 weeks after RD were significantly less than those of sham-operated controls, confirming that renal nerves had been severed. Thus, RD prevented the elevation of blood pressure induced by chronic exposure to cold but had no significant effect on cardiac hypertrophy.

Animals↗

Biological activity and immunological reactivity of human prolactin mutants.

We examined the biological activity and immunological reactivity of four mutants of human PRL. Two were mutants that changed the ability of human PRL to inhibit rat PRL storage when transfected into a rat pituitary cell line:mutations S34A and N31T. Two mutations were in regions of PRL that are highly conserved. One, des(3-11)-PRL, removed the N-terminal cystine loop that most PRLs, except those from certain fish, have, and no GHs have. The other, S90A, mutated a serine that is present in all PRLs but those from some fish and in all GHs. The immunological properties of des(3-11)-PRL were reduced 10-fold compared to those of wildtype human PRL in a RIA using NIH antihuman PRL-3, AFP C11580; the others were similar to those of wild-type PRL. The biological activity of des(3-11)-PRL was the most affected; activity was reduced about 8-fold compared to that of wild-type PRL in the Nb2 cell assay. The activities of the others were similar to that of the wild type. Serine 90 may be partially buried by loops connecting the alpha-helixes. The mutation of serine 90 did not affect the stability of the molecule in vitro, determined by comparing the red shift in tryptophan fluorescence that occurs with increasing concentrations of urea in S90A and wild-type PRL. The activity of S34A and N31T mutations indicates there is no correlation between biological activity and ability to affect storage. The N-terminal cystine loop may be conserved because it is needed for biological activity, but the conservation of serine 90 in GH and PRL must be determined by other properties, such as spacial requirements.

Amino Acid Sequence↗

Follow up of patients after valvular surgery: mail vs. telephone.

A study was undertaken to compare the results of patient follow up done by mail and by telephone. Using valve follow up questionnaires recently received by mail, 100 patients were randomly selected from this group for further follow up by telephone. Interviews were conducted while blinded to the mail response. Patients were questioned as to their functional status (NYHA), improvement as a result of surgery (IMP), incidence of reoperation (REOP) or bacterial endocarditis (SBE) and thromboembolic complications (TE). They were also asked whether they would prefer future follow up by mail or telephone. Analysis using the kappa coefficient and McNemar's test revealed a difference (p < 0.001) in NYHA when comparing mail and telephone responses but no difference in either IMP or TE. There was no incidence of REOP or SBE. Sixty-six percent of patients had no preference in type of future follow up and of the remaining 33%, two-thirds preferred to be contacted by phone. It appears that NYHA is significantly overestimated by the patient whereas the two methods of follow up are comparable when assessing IMP and TE. It should be noted, however, that patients seem to have difficulty in identifying the occurrence of TE and in differentiating between stroke and TIA.

Activities of Daily Living↗

[The human fetal development time table of the major limb bones-ultrasonic bone age].

B-ultrasonic technique was used to examine 297 Chinese fetuses in normal pregnancy woman of completed week age from 12 to 38 weeks. The lengths of the major limb bones were measured and statistical analysis showed that the positive linear correlation between the development of fetuses' limb bones and the completed fetal age is significant.

Bone Development↗

Left ventricular function after mitral valve surgery.

This study examined the effects of various operative procedures on the mitral valve of patients with mitral regurgitation due to degenerative disease of the mitral valve. A randomized clinical trial on the type of annuloplasty ring used at surgery revealed that early postoperative left ventricular systolic function was better in patients who had a flexible ring than in patients who had a rigid ring. Two years after surgery there were no differences between these groups and most patients were found to have fairly normal left ventricular function. The long term results of mitral valve repair in 184 patients revealed a 10-year actuarial survival of 86% +/- 6%. A randomized trial on the effect of preservation of chordae tendineae during mitral valve replacement revealed that the beneficial effect of this procedure on left ventricular function is a lasting one; five years after surgery patients who had mitral valve replacement with preservation of the chordae tendineae have better exercise capacity, and better left ventricular systolic function and performance. The long term results of mitral valve replacement in 154 patients revealed a 10-year actuarial survival of 69% +/- 5%. Logistic regression analysis indicated that age greater than 65 years and complete excision of the native mitral valve were predictors of late mortality. Of those patients, 70 had had chordal preservation during surgery and 84 did not. These two subgroups were remarkably similar preoperatively, but the 10-year actuarial survival was 80% +/- 6% for patients who had chordal preservation and 63% +/- 6% for those who did not. The mitral valve should be repaired whenever possible; if replacement is necessary it should be performed with preservation of the chordae tendineae.

Actuarial Analysis↗

[Scavenging effects of daphnetin and its Cu, Zn complexes on superoxide radical].

The scavenging effects of daphnetin (D) and its Cu, Zn complexes on superoxide radical (O2-.) generated through the photooxidation of riboflavin were studied with human red blood cells (RBC) and RBC membrane as experimental material. The Cu ( II ) complex showed the highest activity. SOD, D and its Cu ( II ), Zn ( II ) complexes were found to have inhibitory effect on the production of lipid peroxide in the membrane, SOD being the best among them.

Erythrocyte Membrane↗

[A study of relation between rheumatoid arthritis (RA) and blood stasis--the effect of acupuncture promoting blood circulation to remove blood stasis].

In this article, the clinical 31 cases patients with Rheumatoid artritis (RA) were observed and animal experiments were carried out on RA model rats and the treatment of acupuncture with combination of the different points was adopted. It was found that most of the 31 cases of RA patients had the signs of bloods stasis and abnormal hemorheology, statistical analysis indicated that there were significant differents between RA patients and healthy person. Red and swelling in joints of four limbs, ear and tail, clubbed toes, abnormal hemorheology, high in blood platelet aggregation and so on were found in model rats of RA, statistically, sinificant differents also exist between model rats of RA and healthy rats. The above indesexes in patients and model rats of RA were significantly improved after acupuncture treatment, which suggested that (1) there be a close relation between RA and blood stasis. (2) acupuncture play a role of promoting blood circulation to remove blood statis. (3) examination of hemorheology may be one of standards that development of RA and curative effect.

Acupuncture Therapy↗

Functional characterization of the promoter for the gene encoding human eosinophil peroxidase.

The molecular basis for commitment of progenitors to the eosinophil lineage and mechanisms by which eosinophil-specific genes are expressed and regulated during differentiation is unknown. Expression of eosinophil peroxidase (EPO) is restricted to the eosinophil lineage. To understand the mechanisms involved in transcriptional regulation of EPO gene expression, we clone the region of the EPO gene upstream of the transcriptional start site and analyzed the cis-acting elements required for EPO promoter activity in an eosinophil-inducible leukemic cell line, HL-60-C15. The 5'-flanking region of the EPO gene containing 1.5 kilobases of sequence upstream of the transcriptional start site was subcloned into the promoterless pXP2-luciferase vector. The EPO-pXP2 construct and 5' deletion mutants were electroporated into HL-60-C15 cells and luciferase reporter activity assessed. The -1.5-kilobase EPO-pXP2 promoter construct reproducibly expressed > 120-fold more luciferase activity than did promoterless pXP2, and a 12-fold (90%) decrease in promoter activity was obtained when sequences between -122 and -45 base pairs (bp) were deleted. The specificity of the EPO promoter for the eosinophil lineage was analyzed by transfecting the EPO-pXP2 constructs and deletion mutants into HL-60-C15 cells and the parental HL-60 line; EPO promoter activity was 8-10-fold less in the HL-60 parental line, suggesting lineage specific elements in the -122 to -45 bp region. To further characterize regulatory sequences important for promoter activity, we performed linker-scanning analysis on the -122 to -45 bp region and identified a number of positively and negatively acting elements in the promoter. DNase I footprinting was performed with HL-60-C15, HL-60, and HeLa nuclear extracts to identify nuclear proteins that may bind to the functional elements; these experiments identified three protected regions of the EPO promoter which correspond to the functional segments defined by linker-scanning analysis and which contain consensus, potential binding sites for Egr-1, H4TF-1, PuF, CTCF, UBP-1, and GaEII transcription factors. Further study of EPO promoter regulation should elucidate unique transcriptional features of eosinophil gene regulation in granulocyte development.

Base Sequence↗

Down syndrome phenotypes: the consequences of chromosomal imbalance.

Down syndrome (DS) is a major cause of mental retardation and congenital heart disease. Besides a characteristic set of facial and physical features, DS is associated with congenital anomalies of the gastrointestinal tract, an increased risk of leukemia, immune system defects, and an Alzheimer-like dementia. Moreover, DS is a model for the study of human aneuploidy. Although usually caused by the presence of an extra chromosome 21, subsets of the phenotypic features of DS may be caused by the duplication of small regions of the chromosome. The physical map of chromosome 21 allows the molecular definition of the regions duplicated in these rare cases of partial trisomy. As a first step in identifying the genes responsible for individual DS features and their pathophysiology, a panel of cell lines derived from 16 such individuals has been established and the molecular break points have been determined using fluorescence in situ hybridization and Southern blot dosage analysis of 32 markers unique to human chromosome 21. Combining this information with detailed clinical evaluations of these patients, we have now constructed a "phenotypic map" that includes 25 features and assigns regions of 2-20 megabases as likely to contain the genes responsible. This study provides evidence for a significant contribution of genes outside the D21S55 region to the DS phenotypes, including the facies, microcephaly, short stature, hypotonia, abnormal dermatoglyphics, and mental retardation. This strongly suggests DS is a contiguous gene syndrome and augurs against a single DS chromosomal region responsible for most of the DS phenotypic features.

Blotting, Southern↗

Analysis of the imperfect octamer-containing human immunoglobulin VH6 gene promoter.

The octamer sequence ATGCAAAT is highly conserved in the promoter of immunoglobulin heavy and light chain genes and is one of the sequence motifs involved in the control of transcription of these genes. The promoter region of an human immunoglobulin heavy chain variable gene, the sole member of the VH6 gene family, was found to differ from other VH gene promoters: it contains neither the conserved octamer motif nor a heptamer sequence, and generally bears little resemblance to other VH gene transcriptional control regions. An imperfect octamer sequence with a single nucleotide substitution (AgGCAAAT) is located 108 bp upstream of the ATG translation start site, and 81 bp upstream of the transcription initiation site. We sought to determine which sequence elements within the VH6 promoter were responsible for transcription initiation by creating progressive deletions of a 1 kb fragment from this region and testing their ability to function as promoter elements in B and non-B cells (HeLa). The minimum fragment required for full promoter function was 110 bp, but a fragment with only 65 bp retained 30-50% activity in B cells. Similar levels of transcription were seen when the -146 bp promoter containing two point mutations in the imperfect octamer was tested. Mutation of a possible pyrimidine box sequence located downstream of the TATA box was shown to have only a minor effect (10-30%) on transcription when three nucleotides were changed. Surprisingly, CAT activity was not B cell-specific, as all constructs had virtually the same activity in several B cell lines and in HeLa cells. Removal of the TATA box led to a 50% reduction in CAT activity, and the region upstream of the TATA box functioned as a promoter in both orientations. The transcriptional activity of the VH6 promoter was virtually enhancer independent: only a minor increase was observed when the immunoglobulin or SV40 enhancer was added to the promoter construct. Electrophoretic mobility shift assays of transcription factor binding to the region around the imperfect octamer indicated that binding was weak when nuclear extracts from either B cells or HeLa cells were used. The amount of complex shifted was increased by mutating the imperfect octamer to a perfect one. Chimeras produced between the VH6 promoter and a B cell-specific promoter from a member of the human VH2 gene family demonstrated that the lack of tissue specificity was due to the absence of a repressor of non-B cell transcription in the VH6 promoter. These results indicate that the VH6 promoter is relatively simple, requiring little more than the TATA element and the imperfect octamer, and transcription from this promoter lacks B cell specificity and is not dependent on the enhancer element.

B-Lymphocytes↗