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Biomedical subjects

S Su

Publications and source records attributed to S Su.

At least 55 records · Page 3Linked to original sources

Evaluation of hydroxyethyl-starch-ferrioxamine as an intravascular MR contrast agent for assessment of myocardial perfusion.

PURPOSE: The present study was carried out to evaluate a new intravascular contrast agent hydroxyethyl-starch-ferrioxamine (HES-FO) for assessment of myocardial perfusion. MATERIAL AND METHODS: Isolated pig hearts were perfused with a crystalloid cardioplegic solution in a Langendorff apparatus. MR images were acquired along the short cardiac axis using T1- and T2*-weighted methods. Gd-DTPA and HES-FO were used as the standard extracellular and test contrast agents, respectively. RESULTS: We found that T1-weighted signal intensity was not significantly affected by HES-FO, but increased significantly in presence of Gd-DTPA. On the other hand, HES-FO resulted in a rapid, transient but significant decrease in T2*-weighted signal intensity. Although Gd-DTPA also decreased T2*-weighted signal intensity considerably, it took much longer for the T2*-weighted signal intensity to return to its initial steady-state with Gd-DTPA than with HES-FO. Moreover, increasing the dose of HES-FO (from 0.0023-0.0138 mmol/kg b.w.) had no effect on the time at which the T2* effect reached its maximum or on the duration of the T2* effect. However, these times and durations were affected significantly by increasing the dose of Gd-DTPA (0.0023-0.027 mmol/kg b.w.). CONCLUSION: The results suggest that HES-FO provides information regarding myocardial vascular flow which cannot be obtained using Gd-DTPA. It is expected that the combined use of intravascular and extracellular type contrast agents will allow more complete assessment of tissue perfusion.

Animals↗

[Digital subtraction angiography and selective arterial embolization in the treatment of vascular tumors in nasopharynx and nasal sinuses].

The paper presents the treatment of vascular tumors in nasopharynx and nasal sinuses with digital subtraction angiography (DSA) and selective arterial embolization. By using preoperative embolization of blood supply arteries, the intraoperative bleeding was reduced significantly, the tumors were shrank and the tumor limits were clear. We recommend that DSA and selective arterial embolization should be used as a routine preoperative method adjunct to surgery for the treatment of vascular tumors of nasopharynx and nasal sinuses.

Adolescent↗

Testing the eukaryotic promoters for efficient expression of exogenous genes in chondrocytes and synoviocytes.

To identify suitable promoters for expressing exogenous genes in arthritic joints, the constitutive, simian virus 40 (SV 40) and IL-1 or metal inducible, human stromelysin and metallothionein (MT) gene promoters were tested for their activity in chondrocytes and synovial fibroblasts. Transient transfection with plasmids containing the reporter chloramphenicol acetyltransferase (CAT) gene attached to these promoters showed that SV40, stromelysin and MT promoters drove CAT expression with different strengths in primary bovine chondrocytes. The MTI-F and MT-IG gene promoters were also functional in human chondrocytes. The SV40, IL-1 inducible stromelysin-1 and MT-IG driven CAT activity was also detectable in human synoviocytes. Therefore, chondrocytes and synoviocytes have the trans-acting factors necessary for transcription from the respective promoters which may be conserved in bovine and human cells. These promoters could be useful for expressing potentially therapeutic anti-inflammatory and anti-erosive genes in arthritic joints.

Animals↗

Tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA is constitutively expressed in bovine, human normal, and osteoarthritic articular chondrocytes.

Tissue inhibitors of metalloproteinases (TIMPs) inhibit the extracellular matrix (ECM) metalloproteinases (MMPs). To determine the source of TIMPs in synovial fluids of patients with osteoarthritis (OA), the ability of chondrocytes to express TIMP-2 and its regulation by agents found in inflammed joints was investigated. The constitutive TIMP-2 mRNA expression was demonstrated in chondrocytes from normal bovine, human OA and normal cartilage. The cross-hybridization of human and bovine TIMP-2 suggested its evolutionary conservation. Serum, IL-1, IL-6 and TGC-beta were unable to augment considerably the basal expression of TIMP-2 mRNA. TIMP-1 RNA expression in chondrocytes from human OA cartilage was elevated compared to non-OA chondrocytes, while TIMP-2 mRNA levels were similar in both. IL-1 beta, IL-6 and TGF-beta did not affect TIMP-2 expression but TGF-beta induced TIMP-1 mRNA in human OA chondrocytes. TIMP-2 and TIMP-1 are therefore differentially regulated in chondrocytes and the basal TIMP-2 levels may be needed for the cartilage ECM integrity.

Animals↗

Regulation of tissue inhibitor of metalloproteinases-3 gene expression by transforming growth factor-beta and dexamethasone in bovine and human articular chondrocytes.

Physiological and pathological degradation of cartilage extracellular matrix (ECM) is regulated by the balance between tissue inhibitors of metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs). We examined the potential of chondrocytes from normal bovine or human osteoarthritic (OA) cartilage to express RNA for the new inhibitor TIMP-3 and studied its regulation by an inducer of matrix synthesis, transforming growth factor-beta (TGF-beta). Freshly released chondrocytes constitutively expressed three transcripts of TIMP-3 that are induced by serum factors. In primary cultures of chondrocytes, one of these factors, TGF-beta, increased TIMP-3 mRNA in a dose-dependent fashion that required de novo protein synthesis and transcription. TGF-beta did not alter stability of the TIMP-3 transcripts in RNA decay time-courses, suggesting a transcriptional control. Nuclear run-on assays confirmed increased rate of TIMP-3 gene transcription by TGF-beta. An antiinflammatory glucocorticoid, dexamethasone, inhibited the basal, and suppressed partially the TGF-beta-inducible, TIMP-3 expression in primary bovine and human chondrocytes. DNA sequencing of bovine TIMP-3 cDNA revealed an open reading frame of a 211-amino-acid protein containing signal peptide and 12 conserved cysteines. The encoded protein differed from human TIMP-3 at four positions. The constitutive expression and evolutionary conservation of TIMP-3 imply its important function. TIMP-3 induction by TGF-beta suggests the role of this factor and TIMP-3 in cartilage remodeling with important implications for arthritis.

Amino Acid Sequence↗

Primary structure of the variable region of monoclonal antibody 2B10, capable of inducing anti-idiotypic antibodies that recognize the C-terminal region of MSA-1 of Plasmodium falciparum.

Previously, we reported on the properties of a monoclonal antibody, 2B10, which has the same determinant on the human erythrocyte as MSA-1 of Plasmodium falciparum (FCR3 strain); the binding of both ligands to erythrocyte receptors was totally sialic acid dependent. In this work, rabbit anti-2B10 idiopathic antibodies were generated. The anti-idiotypic antibodies recognized both the erythrocyte binding site of 2B10 and the C-terminal region of MSA-1 (amino acids 1047 to 1640); they were able to inhibit 2B10 and MSA-1 binding to erythrocytes and partially prevent P. falciparum merozoites from invading erythrocytes. The utility of 2B10 in the study of the interaction between MSA-1 and human erythrocytes prompted us to determine the nucleotide and deduced amino acid sequences of its VH and VL regions. The data show that the 2B10 VH region is part of the J558 family and is especially homologous to BALB/c anti-nitrophenyl monoclonal antibody 21.1.43; the VL region belongs to the VK1 subgroup and comes from the same genomic locus as (NZB x W)F1 anti-DNA and C57BL anti-dextran monoclonal antibodies BXW-14 and 42.48.12.2, respectively. Most of the differences among the VH and VL segments are located in CDR1 and -3. The binding site of 2B10 contains both negatively and positively charged amino acid residues. The amino acid sequences of the 2B10 VH region and a region of MSA-1 from the Wellcome strain of P. falciparum (amino acids 1002 to 1115) share 43% similarity, and the amino acid sequences between the 2B10 VL region and another segment of the same MSA-1 (amino acids 1247 to 1394) share 48% similarity. We conclude that the interactions between erythrocyte receptors and their ligands, 2B10 and MSA-1, are related and that the C-terminal region of MSA-1 is the erythrocyte binding domain.

Agglutination Tests↗

Cell cycle, differentiation and tissue-independent expression of ribosomal protein L37.

A unique human cDNA (hG1.16) that encodes a mRNA of 450 nucleotides was isolated from a subtractive library derived from HeLa cells. The relative expression level of hG1.16 during different cell-cycle phases was determined by Northern-blot analysis of cells synchronized by double-thymidine block and serum deprivation/refeeding. hG1.16 was constitutively expressed during all phases of the cell cycle, including the quiescent phase when even most constitutively expressed genes experience some suppression of expression. The expression level of hG1.16 did not change during terminal differentiation of myoblasts to myotubes, during which cells become permanently post-mitotic. Examination of other tissues revealed that the relative expression level of hG1.16 was constitutive in all embryonic mouse tissues examined, including brain, eye, heart, kidney, liver, lung and skeletal muscle. This was unusual in that expression was not down-modulated during differentiation and did not vary appreciably between tissue types. Analysis by inter-species Northern-blot analysis revealed that hG1.16 was highly conserved among all vertebrates studied (from fish to humans but not in insects). DNA sequence analysis of hG1.16 revealed a high level of similarity to rat ribosomal protein L37, identifying hG1.16 as a new member of this multigene family. The deduced amino acid sequence of hG1.16 was identical to rat ribosomal protein L37 that contained 97 amino acids, many of which are highly positively charged (15 arginine and 14 lysine residues with a predicted M(r) of 11,065). hG1.16 protein has a single C2-C2 zinc-finger-like motif which is also present in rat ribosomal protein L37. Using primers designed from the sequence of hG1.16, unique bovine and rat cDNAs were also isolated by 5'-rapid-amplification of cDNA ends. DNA sequences of bovine and rat G1.16, clones were 92.8% and 92.2% similar to human G1.16 while the deduced amino acid sequences derived from bovine and rat cDNAs each differed by a single amino acid from the sequence of hG1.16 and the published rat L37 sequence. Southern-blot analysis revealed that hG1.16 exists in multiple copies in human, rat and mouse genomes. These G1.16 clones encode unique human, rat and bovine members of the ribosomal protein L37 gene family, which are constitutively expressed even during transitions from quiescence to active cell proliferation or terminal differentiation, in all tissues and all vertebrates investigated.

Amino Acid Sequence↗

Resolving anatomical details in lung parenchyma: theory and experiment for a structurally and magnetically inhomogeneous lung imaging model.

Lung parenchyma is, structurally and magnetically, a very inhomogeneous system. The strong local field gradients due to magnetic susceptibility variation across the air-tissue interfaces impose a spatially dependent phase on spins that are inhomogeneously distributed. As a result, the slice selection process can cause destructive interference and corresponding partial cancellation of the NMR signals from different parts of the slice. The mechanism of this effect was studied by expanding the internal magnetic field gradient as a Fourier series and determining the Fourier components with a foam model, which consists of air bubbles preferentially at the alveolar diameter. The effect of signal cancellation as a function of slice thickness is characterized by a sinc-like function with destructive interference of higher orders shown as lobes and the zeroth order as the main peak. Computer simulation of the slice selection process was conducted to illustrate the combined effects of signal cancellation and spatial average, and their dependence on slice thickness. Finally, images of rat lungs are presented to demonstrate the significant improvement in image quality by avoiding the high order destructive interference of NMR signals in the slice selection process.

Animals↗

A nested case-control study of mammographic patterns, breast volume, and breast cancer (New York City, NY, United States).

The relations of Wolfe mammographic patterns, quantitative mammographic densities, and mammographically estimated breast size to breast cancer risk were investigated prospectively in a case-control study nested in the New York University Women's Health Study, a cohort of 14,291 women in New York City, NY (United States). The archived mammograms of 197 breast cancer cases who were identified during the first 5.5 years of the study and of 521 individually matched controls from the same cohort were retrieved and classified according to Wolfe parenchymal patterns and mammographic densities by two expert radiologists. Breast size and volume were estimated on the mammogram's cranio-caudal projection. In both premenopausal and postmenopausal subjects, the risk of breast cancer increased progressively with increasing density and percent density area. A significantly increased risk was found also for Wolfe pattern DY in premenopausal women and P2 pattern in postmenopausal subjects. In premenopausal women, mammographically determined breast volume and breast height also were associated positively with breast cancer risk. Although the results of the present study confirmed that mammographic parenchymal patterns and densities were important predictors of breast cancer risk, their practical use in screening seems limited due to the high prevalence of high risk patterns.

Adult↗

Prevention of endotoxin-induced acute lethality in Propionibacterium acnes-primed rabbits by an antibody to leukocyte integrin beta 2 with concomitant reduction of cytokine production.

Acute lethality was induced in rabbits by the sequential injection of Propionibacterium acnes and lipopolysaccharide (LPS). P. acnes induced the infiltration of inflammatory cells into the liver lobules during the early phase, and LPS in the late phase caused death in association with pathological changes mimicking hepatocellular necrosis or degeneration around infiltrated mononuclear cells and fibrin deposition in the liver, lung, and kidney, suggestive of a systemic Schwartzman-like reaction. These pathological changes were accompanied by the elevation of plasma tumor necrosis factor (TNF) and interleukin-8 (IL-8) levels. A neutralizing antibody to a leukocyte adhesion molecule, integrin beta 2 (CD18), administered at the time of LPS challenge, prevented reduced the elevation of plasma TNF and IL-8 levels. An anti-TNF alpha antibody but not an anti-IL-8 mediator in this model. These results indicate that CD18 is critically involved in vivo in activating leukocytes to produce cytokines in response to LPS.

Animals↗

Fission yeast TPR-family protein nuc2 is required for G1-arrest upon nitrogen starvation and is an inhibitor of septum formation.

Fission yeast nuc2+ gene encodes a protein of a tetratricopeptide repeat (TPR) family which is conserved throughout evolution. We previously showed that nuc2 is required for exit from the mitotic metaphase. In this study, we present evidence which shows that nuc2 has two additional roles in the cell cycle. We showed that the nuc2 mutant is sterile even at the permissive temperature and septation occurs in the absence of chromosome separation at the restrictive temperature. The nuc2 mutant fails to arrest at the G1 phase upon nitrogen starvation at the permissive temperature which is a prerequisite for conjugation. Upon starvation, however, the nuc2 mutant ceased division normally and induced starvation-dependent gene expression. Therefore, the nuc2 mutant is deficient only for failure to block DNA replication upon starvation. At the lower restrictive temperature, the nuc2 mutant showed a 'cut' phenotype where septation and cytokinesis takes place without the completion of mitosis. Ectopic overexpression of the nuc2+ gene caused multiple rounds of S and M phases in the complete absence of septum formation. We propose that nuc2 is a novel cell cycle regulator essential for three events; firstly for exit from mitosis, secondly for DNA replication restraint under nutrient starvation and thirdly for inhibition of septation and cytokinesis until the completion of mitosis.

Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome↗

Optimization of subtractive hybridization in construction of subtractive cDNA libraries.

The efficiency of subtraction, integrity of residual single-stranded cDNA, and efficient recovery of nanogram quantities of double-stranded cDNA are the three most important factors affecting quality of subtractive hybridization reactions prior to subtractive cDNA library construction. Techniques for efficient isolation of single-stranded cDNA, after subtraction, have greatly improved from early protocols based on hydroxylapatite chromatography to phenol-chloroform extraction of biotin-streptavidin-crosslinked polynucleotides or oligo(dA)-cellulose affinity chromatography. Factors affecting mRNA stability at the hybridization step, however, also have consequences that directly affect the complexity of the library and the length of cDNAs recovered. We have optimized the subtractive hybridization step in subtractive cDNA library construction to ensure that single-stranded cDNAs survive hybridization as near to full length as possible. These improvements have enabled successful construction of subtractive cDNA libraries from the nanogram quantities of single-stranded cDNA remaining after extensive liquid hybridization to high calculated C(o)t values.

DNA, Complementary↗

A monoclonal antibody capable of blocking the binding of Pf200 (MSA-1) to human erythrocytes and inhibiting the invasion of Plasmodium falciparum merozoites into human erythrocytes.

Glycophorin A is a major receptor on human erythrocytes for Plasmodium falciparum, the human malaria parasite. In this work, we have produced four glycophorin A-specific mAb: 2B10, 1E4, 3H12, and 3H2. 2B10 was mapped to the amino terminal region of glycophorin (amino acids 1-31), and its binding to erythrocytes was fully dependent on sialic acid residues. 3H2 bound to the region close to the cell membrane, and its binding to Wr (b-) erythrocytes was significantly decreased, compared with its binding to Wr (b+) erythrocytes. 1E4 and 3H12 recognized sites between those identified by 2B10 and 3H2. Pf200 (MSA-1) is a surface protein on the P. falciparum merozoite which has been shown to bind to erythrocytes. By reciprocal inhibition assays, 2B10 and MSA-1 could be shown to share the same determinant on erythrocytes. Using an in vitro assay, we have shown that 2B10 was the most efficient inhibitor of the invasion of human erythrocytes by P. falciparum merozoites. We conclude that the binding site for MSA-1 is primarily located on the amino terminal region, amino acids 1-31, of glycophorin A, and that 2B10 is valuable for additional study of the interactions between P. falciparum merozoites and human erythrocytes.

Animals↗

Basal and inducible expression of metallothionein and heat shock protein 70 genes in bovine articular chondrocytes.

Human metallothionein (MT) and heat shock protein 70 (hsp70) cRNA probes cross-hybridized with the respective bovine mRNAs under high-stringency conditions, suggesting DNA sequence conservation of the two genes. Released primary bovine articular chondrocytes expressed MT and hsp70 mRNAs constitutively at variable levels, suggesting a possible physiological role of these proteins in cartilage. In first-passage chondrocytes both CdCl2 and ZnCl2 induced MT and hsp70 mRNAs. However, CdCl2 and ZnCl2 were better inducers of hsp70 and MT mRNAs relative to CuCl2. Serum, interleukin-1, and dexamethasone also induced MT but not hsp70 mRNAs. Actinomycin D severely reduced the basal and metal-induced expression of MT and hsp70 mRNAs, suggesting transcriptional control. Inclusion of cycloheximide, an inhibitor of protein synthesis, along with the metal inducers did not influence hsp70 induction but resulted in superinduction of MT mRNA, possibly due to the post-transcriptional stabilization of polysomes. MT and hsp70 induction by metals is therefore independent of de novo protein synthesis. These results demonstrate the potential of articular chondrocytes to express mRNAs for the two stress proteins in response to various physiologically relevant agents by transcriptional and post-transcriptional mechanisms. MTs and hsp70 are likely to have important functions in cartilage metabolism under normal and pathological conditions.

Animals↗

Hemodynamic and nonhemodynamic mechanism of experimental pulmonary edema in rats and the effect of anisodamine and tetramethylpyrazine--electron microscopic observation and measurement of pulmonary arterial, pulmonary arterial wedge and systemic arterial pressure (Part 2).

The pulmonary edema (PE) induced by adrenaline (AD) administration is similar to neurogenic PE. Anisodamine (ADM, 654-2, 30 mg/kg) and tetramethylpyrazine (TMP, 120 mg/kg) have shown significant preventive effects. Electron microscopic observation was carried out to study the changes of microvascular permeability, and the dynamic change of mean pulmonary arterial pressure (PAP, 40 rats), mean pulmonary arterial wedge pressure (PAWP, 20 rats) and mean carotid arterial pressure (CAP) were also measured. The results suggested that both ADM and TMP have significant inhibitory effects on PAWP and CAP increase, as well as on the damage responsible for the increase of microvascular and alveolar permeability.

Adrenergic alpha-Agonists↗

A nontoxic, idiotope vaccine against gram-negative bacterial infections.

Experiments were performed to test the ability of mouse antiidiotopic mAb, specific for an antilipid A mAb, to act as a vaccine against gram-negative bacterial infections. Lipid A is a conserved region of bacterial LPS. Immunization with the antiidiotopic antibodies, coupled to an immunogenic carrier protein (hemocyanin), specifically induced anti-LPS antibody responses in animals from different species. In a mouse model, this immunization resulted in protection against both lethal gram-negative bacteremia and endotoxemia. The antiidiotopic antibodies, however, did not stimulate endotoxin-associated bioactivities, such as induction of TNF and IL-1. These results support the hypothesis that an idiotope vaccine can stimulate beneficial protective immunity against gram-negative infections without the toxicity inherent in LPS.

Animals↗

Effects of human HSS on hepatocyte and hepatoma cell proliferation and D-GAL induced acute liver failure.

Human hepatic stimulator substance (HSS), an organ-specific and heat-stable factor which differs from insulin, glucagon and EGF, has been partially purified from aborted human fetal livers. It was found to stimulate DNA synthesis of human hepatocytes. AH22 hepatoma cells responded dose-dependently. HSS was also found to enhance the survival of D-GAL intoxicated rats as compared to control (62.5% vs. 26.1%). Our results suggest that human HSS is very similar to that in animals.

Animals↗