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Biomedical subjects

S Su

Publications and source records attributed to S Su.

At least 19 recordsLinked to original sources
PubMed1998

Prophylaxis for opportunistic infections among HIV-infected patients receiving medical care.

In 1995 and 1997, the United States Public Health Service (USPHS) and the Infectious Disease Society of America (IDSA) published recommendations for primary prophylaxis of Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC), and toxoplasmosis in HIV-infected adults. We evaluated their implementation at four hospital-based HIV clinics in New York City in patients who initially met the CD4+ criterion for prophylaxis between January, 1995 and April, 1997. Medical records were reviewed at 6-month intervals to determine drugs prescribed. We identified 149 patients for the PCP sample, 130 for MAC, and 138 for toxoplasmosis. In the three samples, 91% were black and Hispanic, 75% to 81% were male, and 43% to 47% had a history of injection drug use (IDU); median age was between 39 and 40 years. PCP prophylaxis was prescribed during 93% of intervals and did not vary significantly by clinic or patient characteristics. Over the study period, MAC prophylaxis increased from 22% to 62%, and prescriptions for macrolides increased from 38% to 87% of all prescriptions. In the logistic regression analysis, prescription for MAC prophylaxis at any time during the study period was less likely in blacks compared with whites (odds ratio [OR] = .08; 95% confidence interval [CI] = .01, .52) and patients attending the clinic with the lowest rate of MAC prophylaxis (clinic D) compared with the clinic with the highest rate (clinic B; OR = .04; 95% CI = .01, .26). Toxoplasmosis prophylaxis was prescribed in 73% of intervals and did not differ significantly by antibody status (p = .42). Prescribing patterns were uniform across gender, HIV risk behavior, and age for PCP and MAC prophylaxis but differed by clinic and race for MAC prophylaxis. Trends in prophylaxis for opportunistic illnesses must continue to be monitored in light of the success of antiretroviral therapy in reducing the morbidity and mortality associated with HIV/AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1998

Chemokines and their role in tumor growth and metastasis.

Chemokines are a superfamily of pro-inflammatory polypeptide cytokines that selectively attract and activate different cell types. Many patho-physiological conditions require the participation of chemokines, including inflammation, infection, tissue injury, allergy, cardiovascular diseases, as well as malignant tumors. Chemokines activate cells through their binding to shared or unique cell surface receptors which belong to the seven-transmembrane, G-protein-coupled Rhodopsin superfamily. The role of chemokines in malignant tumors is complex: while some chemokines may enhance innate or specific host immunity against tumor implantation, others may favor tumor growth and metastasis by promoting tumor cell proliferation, migration or neovascularization in tumor tissue. In this review, the authors summarize some of the recent advances in chemokine research and emphasis is made on the effect of chemokines in tumor growth and metastasis.

Animals↗
PubMed1998

Up-regulation of tissue inhibitor of metalloproteinases-3 gene expression by TGF-beta in articular chondrocytes is mediated by serine/threonine and tyrosine kinases.

The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulates extracellular matrix turn-over in normal animal development, cancer cell metastasis, atherosclerotic plaque rupture and erosion of arthritic cartilage. Transforming growth factor beta (TGF-beta), an inducer of matrix synthesis, potently enhances mRNA and protein of a recently characterized MMP inhibitor, TIMP-3, in bovine articular chondrocytes. We examined the implication of protein kinases in the TGF-beta-mediated induction of TIMP-3 expression by utilizing activators and inhibitors of these enzymes. Protein kinase A activators, dibutyryl cyclic AMP, or forskolin had little or no effect, respectively, while phorbol 12-myristate 13-acetate (PMA), a PKC activator, increased TIMP-3 gene expression. H7, a serine/threonine protein kinase inhibitor, markedly reduced the response of TIMP-3 gene to TGF-beta. Furthermore, two protein tyrosine kinase inhibitors, genistein and herbimycin A, inhibited TGF-beta induction of TIMP-3. H7 and genistein also suppressed TGF-beta-induced TIMP-3 protein expression. These results suggest that TGF-beta signaling for TIMP-3 gene induction involves H7-sensitive serine/threonine kinase as well as herbimycin A- and genistein-sensitive protein tyrosine kinases.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

Urinary levels of chemokines (MCAF/MCP-1, IL-8) reflect distinct disease activities and phases of human IgA nephropathy.

Leukocytes have been implicated to be involved in the pathogenesis of IgA nephropathy (IgAN). To clarify the precise molecular mechanism of recruitment and activation of leukocytes in the subgroups of IgAN, latent, acute, and chronic types, we studied monocyte chemotactic and activating factor (MCAF/MCP-1) and interleukin (IL)-8 in urines and renal expression of these cytokines. Urinary MCAF levels were significantly higher in chronic type, and were correlated with pathological progressive factors such as mesangial proliferation and interstitial cellular infiltration associated with CD68-positive macrophage. On the other hand, urinary IL-8 elevated only in acute type and were correlated with glomerular endocapillary proliferation and the degree of hematuria. In immunohistochemical study, IL-8 was mainly observed in glomeruli, otherwise MCAF in vascular endothelial cells, tubular epithelial cells, and infiltrated mononuclear cells in the interstitial lesions. These observations demonstrated that MCAF and IL-8 were differentially expressed in kidneys with IgAN, and their subtypes, and suggest that chemokines may be involved in the pathogenesis of IgAN at distinct phases or pathological lesions, possibly through the recruitment and activation of a distinct type of leukocyte.

Adolescent↗
PubMed1998

Diffusion- and T2-weighted increases in magnetic resonance images of immature brain during hypoxia-ischemia: transient reversal posthypoxia.

Hypoxic-ischemic changes in brain are detected earlier with diffusion-weighted (DW) than with T2-weighted magnetic resonance (MR) imaging techniques in adults, whereas the response in immature brain is not known. We investigated MR imaging changes prior to, during, and/or after 2 h of hypoxia-ischemia (right carotid artery occlusion + 2 h of hypoxia) in 7-day-old rats anesthetized with isoflurane. In general, within the first 45 min of hypoxia-ischemia there were no changes in the DW or T2-weighted images. By the second hour of hypoxia-ischemia there were marked areas of increased intensity in both the T2 and the DW images, with cortex and striatum being affected prior to thalamus and hippocampus. The area of DW exceeded that of T2 hyperintensities. In the first hour after hypoxia-ischemia there was a transient recovery of hyperintensities on both T2 and DW images. Between 24 and 72 h the hyperintense area on DW images decreased, whereas that on T2-weighted images increased. The distribution of pathological damage assessed histologically correlated with the areas of hyperintensity on the MR images. In contrast to adult brain, early hypoxic-ischemic injury in immature brain is detected as an increase in intensity in both diffusion- and T2-weighted images, indicating a unique alteration in brain water dynamics in this neonatal model of hypoxia-ischemia. These imaging changes and alterations in brain water can rapidly but transiently reverse upon the start of normoxia and reperfusion, suggestive of secondary energy failure or delayed neuronal death.

Aging↗
PubMed1998

Chemokines, receptors, and their role in cardiovascular pathology.

A superfamily of leukocyte chemotactic proteins, known as chemokines, has been identified during the past decade. Chemokines selectively attract and activate different leukocyte subpopulations and are key mediators of a variety of patho-physiological states, including hematopoiesis, inflammation, infection, allergy, atheroslerosis, reperfusion injury, as well as malignant tumors. Chemokines bind and activate a number of specific or promiscuous, G-protein-coupled seven-transmembrane receptors. Some of these receptors are utilized by human immuno-deficiency virus type 1 as essential fusion co-factors. Further understanding of the role of chemokines and their receptors in host defense will help develop means by which the beneficial versus detrimental effects of these molecules can be balanced.

Arteriosclerosis↗
PubMed1998

Regulation of placental monocyte chemotactic and activating factor during pregnancy and chorioamnionitis.

A number of placental cytokines participate in the feto-maternal defence mechanism. Monocyte chemotactic and activating factor (MCAF) is one of these chemokines. We investigated the pattern of placental MCAF production, the localization of MCAF-producing cells in the placenta, and alterations in its expression in chorioamnionitis. The amounts of MCAF protein produced by the placenta increased during pregnancy irrespective of the presence of uterine contraction. MCAF mRNA was expressed at equivalent levels in the first and second trimester placenta, but at higher levels in the third trimester placenta. Chorioamnionitis in the third trimester placenta induced a 10-fold increase in MCAF protein production and a 3-fold increase in MCAF mRNA level. Immunohistochemical analysis of the placenta revealed the MCAF-producing cells to be trophoblasts. Stimulation of placental cells with lipopolysaccharide augmented MCAF production. These results indicate unique transcriptional and developmental regulation of MCAF mRNA and protein production during pregnancy and chorioamnionitis. Placental MCAF may be involved in the feto-maternal defence mechanism by activating feto-placental and maternal monocytes in chorioamnionitis.

Blotting, Western↗
PubMed1997

Identification of rapid turnover transcripts overexpressed in thyroid tumors and thyroid cancer cell lines: use of a targeted differential RNA display method to select for mRNA subsets.

The mRNAs of transiently expressed proteins such as cytokines and proto-oncogenes are commonly subject to rapid transcriptional activation and degradation. Transcript turnover is determined in part by association of certain proteins with consensus AU-rich motifs (AUUUA) in the 3'-untranslated region of the transcripts. Here we report a modification of differential RNA display (DRD) to detect differentially expressed rapid turnover mRNAs containing AU-rich motifs from thyroid cancer tissues and cell lines. RNA of normal and thyroid cancer tissues was differentially displayed using a 3'anchor primer to the poly(A) tail and an arbitrary 5'primer incorporating an AUUUA sequence. The appropriateness of the strategy was established by its ability to display known early response genes, such as c- fos, using partially degenerate primers. To test whether the novel cDNAs isolated coded for transcripts subject to rapid turnover, they were used as probes for Northern blots of RNA from clonal human thyroid carcinoma cell lines treated for varying periods with either cycloheximide or actinomycin D. A number of novel differentially expressed cDNA fragments were isolated from human papillary thyroid carcinoma tissues, among them a cDNA with zinc finger motifs and homology to other zinc finger proteins. Using this fragment to probe a cDNA library, a full-length cDNA (ZnF20) was isolated that was 4333 bp in length and contained an open reading frame of 1029 amino acids. The ZnF20 cDNA hybridized to multiple transcripts in a thyroid cancer cell line (8.0, 4.5 and 2 kb) that increased after cycloheximide treatment and decayed <2 h after addition of actinomycin D. The ZnF20 mRNA was overexpressed in three of six thyroid papillary carcinomas as compared with paired normal thyroid tissue controls. The data presented here support the use of a targeted DRD approach for the isolation of rapid turnover mRNAs, many of which may be interesting candidate oncogenes.

Amino Acid Sequence↗
PubMed1997

Inhibition of immature erythroid progenitor cell proliferation by macrophage inflammatory protein-1alpha by interacting mainly with a C-C chemokine receptor, CCR1.

Several lines of evidence indicate that macrophage inflammatory protein-1alpha (MIP-1alpha) modulates the proliferation of hematopoietic progenitor cells, depending on their maturational stages. To clarify the mechanisms for the modulation of hematopoiesis by this chemokine, we examined the expression of a receptor for MIP-1alpha, CCR1, on bone marrow cells of normal individuals using a specific antibody and explored the effects of MIP-1alpha on in vitro erythropoiesis driven by stem cell factor (SCF) and erythropoietin (Epo). CCR1 was expressed on glycophorin A-positive erythroblasts in addition to lymphocytes and granulocytes. CCR1+ cells, isolated from bone marrow mononuclear cells (BMMNCs) using a cell sorter, comprised virtually all erythroid progenitor cells in the BMMNCs. Moreover, MIP-1alpha inhibited, in a dose-dependent manner, colony formation by burst-forming unit-erythroid (BFU-E), but not by colony forming unit-erythroid (CFU-E), in a methylcellulose culture of purified human CD34+ bone marrow cells. Although reverse-transcription polymerase chain reaction (RT-PCR) showed the presence of CCR1, CCR4, and CCR5 transcripts in CD34+ cells in BM, anti-CCR1 antibodies significantly abrogated the inhibitory effects of MIP-1alpha on BFU-E formation both in a methylcellulose culture and in a single cell proliferation assay of purified CD34+ cells. Although the contribution of CCR4 or CCR5 cannot be completely excluded, these results suggest that MIP-1alpha-mediated suppression of the proliferation of immature, but not mature erythroid progenitor cells, is largely mediated by CCR1 expressed on these progenitor cells.

Analysis of Variance↗
PubMed1997

Analyses of the stability and function of three surface mutants (R82C, K69H, and L32R) of the gene V protein from Ff phage by X-ray crystallography.

The high-resolution crystal structure of the gene V protein (GVP) from the Ff filamentous phages (M13, fl, fd) has been solved recently for the wild-type and two surface mutant (Y41F and Y41H) proteins, leading to a plausible model for the polymeric GVP-ssDNA complex (Guan Y, Zhang H, Wang AHJ, 1995, Protein Sci 4:187-197). The model of the complex shows extensive contacts between neighboring dimer GVPs involving electrostatic interactions between the K69 from one and the D79 and R82 from the next dimer. In addition, hydrophobic interactions between the amino acids L32 and L44 from one and G23 from the next dimer also contribute to the dimer-dimer interactions. Mutations at the L32, K69, and R82 amino acid sites generally destabilize the protein and many of these affect the function of the phage. We have studied the structural effects of three mutant proteins involving those sites, i.e., L32R, K69H, and R82C, by X-ray crystallographic analysis at 2.0 A resolution. In L32R GVP, the structural perturbation is localized, whereas in K69H and R82C GVPs, some long-range effects are also detected in addition to the local perturbation. We have interpreted the protein stability and the functional properties associated with those mutations in terms of the observed structural perturbations.

Amino Acid Sequence↗
PubMed1997

Assessment of retrograde cardioplegia with magnetic resonance imaging and localized 31P spectroscopy in isolated pig hearts.

OBJECTIVE: This study was done to determine whether retrograde delivery of cardioplegic solution provides uniform blood flow to the myocardium supplied by an occluded coronary artery and whether it maintains myocardial energy levels beyond the coronary occlusion. METHODS: Isolated pig hearts were used. A hydraulic occluder was placed at the origin of the left anterior descending coronary artery. The perfusion pressure for retrograde delivery of cardioplegic solution was controlled at 40 to 50 mm Hg. Magnetic resonance imaging and localized 31P magnetic resonance spectroscopy were used to assess myocardial perfusion and energy metabolism, respectively. RESULTS: Magnetic resonance perfusion images (n = 7) showed that the perfusion defect that occurred during antegrade delivery of cardioplegic solution (as a result of the occlusion of the left anterior descending coronary artery) resolved during retrograde delivery of cardioplegic solution. Retrograde perfusion delivered similar amounts of flow to the jeopardized myocardium as it did to other areas of the myocardium. However, the distribution of cardioplegic solution by the retrograde route was heterogeneous (cloudlike) across both ventricular walls. 31P magnetic resonance spectra showed that the ischemic changes induced by occlusion of the left anterior descending artery during antegrade perfusion were greatly alleviated by retrograde perfusion; however, it took longer for retrograde cardioplegia (n = 7, 17.08 minutes) to restore the levels of inorganic phosphate/phosphocreatine relative to the effect of releasing the left anterior descending artery occluder during antegrade delivery of cardioplegic solution (n = 7, 5.3 minutes). CONCLUSIONS: First, retrograde delivery of cardioplegic solution provides sufficient flow to the myocardium beyond a coronary occlusion to maintain near normal levels of energy metabolites, and second, the efficacy of the retrograde route of cardioplegic solution delivery (in terms of distribution of the solution and rate of myocardial energy recovery) is significantly lower than that of the antegrade route.

Animals↗
PubMed1997

Saccharide anions as inhibitors of the malaria parasite.

The asexual erythrocytic stage of Plasmodium falciparum was grown in culture in the presence or absence of glycoconjugate polyanions of varying structure, size and substitutions. Heparin, dextran sulfate, fucoidan and pentosan polysulfate had antimalarial IC50 values between one and 11 microg ml(-1). Constituent heparin disaccharides were ineffective against the malaria parasite and desulfation from either the O- or N-substitution sites of heparin or reduction of the uronic acid carboxyl group neutralized the antimalarial response to varying degrees. Immobilization of heparin onto agarose beads still permitted antimalarial activity suggesting that parasite uptake of the glycoconjugate is not required for inhibition. Accordingly, it is concluded that invasion of free parasites into the erythrocytes was inhibited rather than parasite maturation within the red cell. Merozoite surface antigen-1 was apparently prevented from binding to human erythrocytes in the presence of highly sulfated polyanions and, in a dose-dependent fashion, heparin.

Animals↗
PubMed1997

High-throughput RT-PCR analysis of multiple transcripts using a microplate RNA isolation procedure.

We have developed a high-throughput, multiplex reverse transcription PCR (RTPCR) assay that is suitable for the analysis of medium-to low-copy cellular RNA transcripts from small numbers of cells (10(4)). High throughput was attained by utilizing microplate-based RNA extraction and RTPCR protocols, followed by PCR product visualization of a multiwelled agarose gel, stained with SYBR Green I dye. The transcriptional assay was unaffected by solvents (dimethyl sulfoxide and methanol) routinely used in high-throughput drug screens at concentrations required for compound solubilization. Furthermore, it has been used successfully for the investigation of differential mRNA expression levels of tumor necrosis factor alpha (TNF-alpha) and Interleukin-1 beta (IL-1 beta) in lipopolysaccharide (LPS)-stimulated THP-1 cells (a human monocytic cell line) and the identification of specific IL-1 beta transcriptional inhibitors.

Benzothiazoles↗
PubMed1997

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↗
PubMed1997

[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↗
PubMed1996

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↗
PubMed1996

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↗