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Biomedical subjects

A C Chang

Publications and source records attributed to A C Chang.

At least 55 records · Page 3Linked to original sources
PubMed1999

Immunohistologic evaluation of mechanisms mediating hyperacute lung rejection, and the effect of treatment with K76-COOH, FUT-175, and anti-Gal column immunoadsorption.

Although most investigators agree that lung dysfunction occurs rapidly in various pig-to-primate hyperacute lung rejection (HALR) models, the basic mechanisms mediating this phenomenon remain in question. Here we describe an immunohistochemical method for assessment of mechanisms driving HALR. Using an established model wherein piglet lungs are perfused ex vivo with human blood, six experimental groups (K76 COOH; FUT-175; K76 with FUT; anti-alpha-Gal column adsorption; column with FUT; and column with K76) and two control groups (unmodified human blood; autologous pig blood) were studied. Each lung was biopsied serially during perfusion, and assessed using an immunohistochemical technique, with vWF staining as an internal control to quantitate binding of human IgM, IgG, C3, C5b-9, properdin, and C1q. The effect of each treatment and subsequent lung perfusion on IgG and IgM anti-alpha-Gal titers(by ELISA) and on pig endothelial cell cytotoxicity were correlated with histologic findings. We found that [1] the classical complement activation pathway was activated, as has been shown for other pig organs in primate or human blood environments [2]; alternative complement pathway activation is also seen, which has not been described for other organs in pig-to-primate models, but only in the context of classical pathway activation; and [3] anti-Gal column absorption, pharmacologic inhibition of complement, or combination therapy each was associated with histologic evidence of partial protection, consistent with what would be predicted for each intervention. Further, immunohistologic differences correlated with physiologic outcomes [8] and with antibody assay results, and revealed that treatments used were incompletely effective. Our data suggest that more complete inhibition of antibody- and complement-driven pathways than was achieved in these experiments will be necessary to prevent the antibody and complement-mediated facets of hyperacute lung rejection. This immunohistologic technique may also help us identify additional pathogenic mechanisms important to eventual clinical application of pig-to-human lung xenografts.

Acute Disease↗
PubMed1999

Impact of respiratory syncytial virus infection on surgery for congenital heart disease: postoperative course and outcome.

OBJECTIVES: a) To describe the postoperative course and outcome of cardiac surgery in children with recent respiratory syncytial virus (RSV) infection; and b) to evaluate whether timing of surgery has any impact on the outcome. DESIGN: Retrospective case series. SETTING: Intensive care unit and medical and surgical wards of a teaching pediatric hospital. PATIENTS: Twenty-five children (aged 25 days to 3.5 yrs; median, 4 months) with congenital heart disease who had cardiac surgery within 6 months after RSV infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We reviewed the clinical course and outcome of all patients. The cardiac diagnoses included ventricular septal defect (n = 11), tetralogy of Fallot (n = 3), atrioventricular canal (n = 3), and others (n = 8). Thirteen patients had surgery during the same admission as RSV infection (group I), and 12 patients had surgery electively after being discharged to home after RSV infection (group II). Two patients in group I died; both of these patients had undergone total repair of tetralogy of Fallot within 2 wks after admission for RSV infection. Postoperative complications in group I patients included pulmonary hypertension (n = 5), adult respiratory distress syndrome (n = 1), tracheal stenosis (n = 1), left ventricular dysfunction (n = 1), pericardial effusion (n = 1), secondary bacterial or fungal infection (n = 7), and deep venous thrombosis (n = 1). Of all group I patients, the ones who were operated on early appeared to be at higher risk for complications, especially for postoperative pulmonary hypertension. No patient in group II died, and only two patients had minor complications (one had reactive airway disease, and the other had a transient superior vena cava syndrome after a bidirectional Glenn operation). CONCLUSIONS: Cardiac surgery performed during the symptomatic period of RSV infection is associated with a high risk of postoperative complications, especially postoperative pulmonary hypertension. These complications appeared to be more frequent and of greater severity in patients who had earlier surgery compared with those who had later surgery. More studies are needed regarding the proper timing of cardiac surgery in patients with congenital heart disease and RSV infection.

Cardiac Surgical Procedures↗
PubMed1999

Seroprevalence of CMV antibodies in a blood donor population and premature neonates in the south-central Taiwan.

Infection of cytomegalovirus (CMV) via contaminated blood may endanger immunocompromised patients that require transfusion therapy. The aim of this study is to determine the prevalence of CMV antibodies in the blood donor population in Southern-central Taiwan. A total of 1800 consecutive sera, obtained from Tainan Blood Center of Chinese Blood Services Foundation (CBSF), were tested for CMV antibodies by two commercial enzyme immunoassays (EIAs). Of the sera tested, 150 (8.3%) were found to be CMV seronegative. The frequency of CMV seropositivity revealed no significant difference between male and female donors. The frequency of CMV seronegativity showed a stepwise decrease with the increase of donor age. In addition, the prevalence of HBsAg, antibodies to hepatitis C virus (anti-HCV), antibodies to human immunodeficiency viruses type 1 and 2 (anti-HIV 1 + 2) and antibodies to human T-cell lymphotropic viruses type I and II (anti-HTLV I/II) were compared between CMV seropositive and seronegative groups. Our results showed that there was no significant difference in seroprevalence of these markers between CMV seropositive and seronegative groups. Our findings also showed that six out of twenty (30.0%) premature neonates were CMV-seropositive. These premature specimens and those EIA discrepancy samples were confirmed by specific nucleic acid amplification using polymerase chain reaction (PCR). Our results suggest that a program which aims to supply CMV seronegative blood or blood components to the patients, should not solely depend on current antibody screening methods in an area where CMV infection is highly endemic. Amendments such as PCR testing, leukocyte reduction by filtration before transfusion may be more practical.

Adolescent↗
PubMed1998

Synthesis and transporter binding properties of (R)-2 beta, 3 beta- and (R)-2 alpha, 3 alpha-diaryltropanes.

(R)-2-Aryl-2-tropinone (9) was synthesized from (R)-2-carbomethoxy-3-tropinone (5) and was used as the key intermediate for the synthesis of (R)-2 beta, 3 beta- and (R)-2 alpha, 3 alpha-diaryltropanes. Inhibition of radioligand binding studies at the dopamine, serotonin, and norepinephrine transporters showed that the (R)-3 beta-(4-methylphenyl)-2 beta-phenyltropane (3b, RTI-422) possessed an IC50 value of 1.96 nM at the dopamine transporter and was highly selective for this transporter relative to the serotonin and norepinephrine transporters.

Carrier Proteins↗
PubMed1998

gas7: A gene expressed preferentially in growth-arrested fibroblasts and terminally differentiated Purkinje neurons affects neurite formation.

Growth arrest-specific (gas) genes are expressed preferentially in cells that enter a quiescent state. gas7, which we identified in serum-starved murine fibroblasts, is reported here to be expressed in vivo selectively in neuronal cells of the mature cerebral cortex, hippocampus, and cerebellum. gas7 transcripts encode a 48-kDa protein containing a structural domain that resembles sequences of OCT2, a POU transcription factor implicated in neuronal development, and synapsins, which have a role in modulating neurotransmitter release. Using in situ hybridization and immunocytochemical analysis, we show that GAS7 expression occurs prominently in cerebellar Purkinje cells and that inhibition of production in terminally differentiating cultures of embryonic murine cerebellum impedes neurite outgrowth from maturing Purkinje cells. Conversely, GAS7 overexpression in undifferentiated neuroblastoma cell cultures dramatically promotes neurite-like outgrowth. Collectively, our results provide evidence for an association between expression of this gas gene and neuronal development.

Amino Acid Sequence↗
PubMed1998

Identification of a second stanniocalcin cDNA in mouse and human: stanniocalcin 2.

It has recently been shown that mammals contain a gene encoding a protein that is related to stanniocalcin (STC), a hormone previously considered to be present only in bony fish where it plays a major role in Ca2+ homeostasis. Here we report the identification in the mouse and human of a cDNA, STC-2, that shows significant similarity to the first mammalian STC (which we now rename STC-1). Northern analysis revealed that mammalian STC-2, like STC-1, is expressed in a wide variety of tissues. In contrast to STC-1, the predicted amino acid sequence of STC-2 contains a cluster of histidine residues in the C-terminal portion of the protein, which suggests that STC-2 may interact with metal ions.

Alternative Splicing↗
PubMed1998

Active site inhibited factor VIIa (DEGR VIIa) attenuates the coagulant and interleukin-6 and -8, but not tumor necrosis factor, responses of the baboon to LD100 Escherichia coli.

Antitissue factor antibody attenuated the coagulopathic and lethal responses to LD100 Escherichia coli, whereas active site inhibited factor Xa inhibited only the coagulopathic response. In this study, we wished to determine: (1) whether active site inhibited factor VIIa blocks the coagulopathic and/or attenuates the lethal effects of LD100 E coli and (2) whether these effects are accompanied by attenuation of the inflammatory cytokine response to LD100 E coli. Eight baboons infused for 2 hours with LD100 E coli also were given five bolus infusions of DEGR VIIa of 280 microg/kg at T = -10 minutes, +2, 4, 6, and 8 hours and observed for changes in vital signs, and the concentrations of hemostatic components (fibrinogen, platelets, fibrin degradation products) and inflammatory mediators (tumor necrosis factor [TNF], interleukin-6 [IL-6], IL-8) at T = 0, 1, 2, 4, 6, and 8 hours. Eight control baboons were also infused with LD100 E coli alone and followed as described above. Four of the eight baboons treated with DEGR VIIa were permanent 7-day survivors versus none in the control group. The mean survival times for the treated and control groups were 116 +/- 22 and 26 +/- 8 hours, respectively. These values differed significantly from each other, (P = .0008). The decrease in platelet and fibrinogen concentrations and the increase in fibrin degradation products observed in the control group were significantly attenuated in the treated group, as was thrombosis of renal glomerular capillaries. Treatment with DEGR VIIa showed no effect on the peak TNF response to LD100 E coli at T = 2 hours (170 +/- 32 v 120 +/- 35 ng/mL). DEGR VIIa, however, did attenuate the IL-6 and IL-8 responses at T = 8 hours (ie, the IL-6 concentrations were 81 +/- 10 for treated and 1,256 +/- 236 for the control groups and the IL-8 concentrations were 28 +/- 3.9 for the treated and 60 +/- 8.2 for the control group). These values for IL-6 and IL-8 differed significantly from each other between the treated and control groups (P = .0001 and .0074, respectively). It should be noted that the initial responses of IL-6 and IL-8 up to T = 4 hours were not attenuated. We concluded that DEGR VIIa treatment attenuates inflammatory, as well as hemostatic system responses to LD100 E coli. We hypothesize that this occurs through interference with the assembly and/or interactions of tissue factor/VIIa complexes.

Animals↗
PubMed1998

Human stanniocalcin (STC): genomic structure, chromosomal localization, and the presence of CAG trinucleotide repeats.

Stanniocalcin (STC) is a glycoprotein hormone that is secreted by the corpuscle of Stannius, an endocrine gland of bony fish. It prevents hypercalcemia via mechanisms including inhibition of calcium uptake across the gills. Mammalian homologues have recently been reported but their function is unknown. Here we report the genomic organization and the transcription start site of the human STC gene and the existence of a polymorphic CAG trinucleotide repeat complex within the 5' untranslated region (UTR) of the mRNA and a smaller [CAG]6 repeat in the 3' UTR. As CAG repeats are associated with various human diseases, we used dual-color fluorescence in situ hybridization to localize the STC gene near markers D8S131 and D8S339 on chromosome 8p11.2-p21. STC should be considered a candidate gene for hereditary diseases mapped to this region.

Base Sequence↗
PubMed1998

Differential display of mRNA.

Differential display of mRNA (DD) is a technique in which mRNA species expressed by a cell population are reverse transcribed and then amplified by many separate polymerase chain reactions (PCR). PCR primers and conditions are chosen so that any given reaction yields a limited number of amplified cDNA fragments, permitting their visualization as discrete bands following gel electrophoresis. This robust and relatively simple procedure allows identification of genes that are differentially expressed in different cell populations. Here we review DD including some recent modifications, and compare it with other techniques for analyzing differential mRNA expression.

DNA Primers↗
PubMed1998

Transcatheter closure of an extracardiac Fontan fenestration.

As the extracardiac Fontan operation evolves, a reliable method for creating and subsequently closing communications between the systemic and pulmonary venous chambers would be useful. We describe a surgical technique for creating this "fenestration" and a complementary transcatheter technique that allows safe and reliable closure of these communications regardless of size and position.

Anastomosis, Surgical↗
PubMed1998

Video-assisted cardioscopy for left ventricular thrombectomy in a child.

Left ventricular thrombus is a complication of myocardial infarction, ventricular aneurysm, cardiomyopathy, and myocarditis. Left ventriculotomy has been the standard approach for removal of left ventricular thrombus. This approach has produced an unacceptable incidence of ventricular dysfunction, arrhythmias, and aneurysm formation. We describe a case of left ventricular thrombus with systemic embolization in a patient with myocarditis. Video-assisted cardioscopy allowed visualization and removal of the thrombus via an aortotomy, thereby avoiding a left ventriculotomy.

Adolescent↗
PubMed1998

Protein kinase C isoforms during the development of deciduomata in pseudopregnant rats.

In this study, we determined the expression of protein kinase C (PKC) isoforms during trauma-induced decidualization. The findings revealed that at least five PKC isoforms (alpha, delta, zeta, iota and lambda) were present in both control and decidualized tissues. After trauma-stimulation, PKC alpha was down-modulated in the deciduomata but not in the myometrium. Down-modulation was compatible with the increase in cell mitosis which reached a maximum at 2-3 days. On the other hand, PKC zeta was not down-modulated. It was increased both in the deciduomata and myometrium, and paralleled the frequency of decidual cell mitosis. The PKC isoforms of delta, iota and lambda were also increased, but they were associated with the depression of cell mitosis. Therefore, these findings suggested that the variable expression of PKC isoforms in trauma-induced decidualizing tissue in pseudopregnant rats may be involved in the modulation of decidual cell growth.

Animals↗
PubMed1998

Production and characterization of monoclonal antibodies against Tal1 oncoprotein.

TAL1 (or SCL) oncogene functions as a transcription regulatory factor that is necessary for the early development of all hematopoietic lineages. Aberrant expression of Tall protein in T cells is the cause of T-cell acute lymphoblastic leukemia (T-ALL) in children. We generated two hybridomas that secreted monoclonal antibodies (MAbs) that reacted strongly with GST-TAL(1-210) but not with GST fusion protein in ELISA assay. These two MAbs, TWN3 and TWN60, recognized TALI oncoprotein expressed in transfected COS-1 cells by Western blotting. In addition, both MAbs were also effective in detecting TAL1 oncoprotein in leukemic cells by immunoprecipitation and immunocytochemistry. Therefore, they should be useful in the studies of Tall protein functions in both hematopoietic development and oncogenesis.

Animals↗
PubMed1998

Complement inhibition by FUT-175 and K76-COOH in a pig-to-human lung xenotransplant model.

Two complement inhibitors, FUT-175 (FUT) and K76-COOH (K76), were studied as single agents in an ex vivo, in situ model of pig lung rejection by human blood. Pulmonary toxicity (primarily increased pulmonary vascular resistance [PVR]) was seen with FUT at a dose which inhibited complement in vitro (0.4 mg/ml); a lower dose (0.1 mg/ml) was therefore used. K76 had little apparent toxicity at a dose which inhibited complement in vitro (6 mg/ml), but activated complement, leading to C3a elaboration. Efficacy was then assessed by 1) deposition of complement pathway components in the lung and 2) lung survival during perfusion with human blood. Neither agent consistently prolonged median lung survival (FUT: 50 min. +/- 28 SEM; K76: 37 +/- 16), blocked thromboxane production, or prevented PVR elevation compared to experiments using unmodified human blood (survival 9 min. +/- 2). At the doses used, both agents prevented deposition of terminal complement complex (TCC) in the lung. This finding demonstrates that the various phenomena associated with hyperacute lung rejection (thromboxane release, PVR elevation, capillary leak, and intraalveolar hemorrhage) can all occur despite abrogation of membrane attack complex formation. We can not exclude a contribution by drug toxicity or complement damage (mediated by C3a or other complement pathway components proximal to TCC) to the observed lung injury. We conclude that, although both FUT and K76 inhibit deposition of TCC in the lung, at the dose tested neither drug is useful as a single agent to prolong survival in a pig-to-human lung xenograft model.

Animals↗
PubMed1998

Lupus humoral autoimmunity induced in a primate model by short peptide immunization.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by humoral autoimmunity against the spliceosomal proteins, including Sm B/B'. In SLE patients with anti-Sm B/B' antibodies the proline rich sequence, PPPGMRPP, is the predominant Sm B/B' autoimmune epitope and appears to be an early target in the development of the anti-Sm B/B' response. METHODS: Two female baboons were immunized with the PPPGMRPP peptide from the Sm B/B' spliceosomal protein constructed on a MAP backbone in Freund's adjuvant. One female control baboon was immunized with Freund's adjuvant alone. Baboon sera were collected and assessed for antibody binding to the spliceosomal proteins and compared to SLE patient and control sera. RESULTS: Peptide immunized baboons developed antibodies to multiple regions of the Sm B/B' protein, as well as reactivity against other spliceosomal proteins. Consistent with serologic manifestations found in SLE, experimental baboons also acquired anti-nuclear antibodies, anti-nuclear ribonucleoprotein (nRNP) antibodies and, in one animal, anti-double stranded DNA antibodies. The control animal had none of these immunologic findings. CONCLUSIONS: Immunization with PPPGMRPP is capable of initiating a humoral autoimmune response in primates against the Sm, nRNP complex from which the peptide was derived. The additional autoantibody specificities generated in experimental animals are similar to those found in human SLE sera. This study is the first evidence of peptide induction of SLE humoral autoimmunity in a primate model.

Amino Acid Sequence↗
PubMed1998

Biodegradable polymer microspheres as vaccine adjuvants and delivery systems.

Though vaccination has been the most cost-effective way of controlling infectious diseases, the logistics of delivering at least two to three doses of conventional vaccines for primary immunization to achieve protection are difficult and compliance is frequently inadequate, particularly in developing countries. In recent years biodegradable polymer microspheres have received much attention for the purposes of controlled release of antigens, (i) to reduce the number of doses needed for primary immunization to as few as a single dose and (ii) to target an antigen to microfold cells on mucosal surfaces after oral administration or to antigen-presenting cells after parenteral inoculations. A variety of vaccine antigens have been encapsulated in microspheres usually composed of poly (lactic/glycolic) acid (PLGA). Based on the size of the microspheres, molecular weight of polymer and ratio of lactic to glycolic acid in the polymer, the antigen may be targeted to various cells of the immune system or it may form a depot at the site of injection, allowing the slow release of the antigen for extended periods. Additionally, another adjuvant may be incorporated inside microspheres together with the antigen, further enhancing or modulating the immune response to the desired type. The major problems in developing controlled-release vaccines include instability of vaccine antigens during micro-encapsulation, storage and subsequent hydration. We encapsulated tetanus toxoid (TT) and Haemophilus influenzae type b capsular polysaccharide conjugated to TT (Hib-T) inside PLGA microspheres and evaluated the antibody levels in mice. A single injection of these micro-encapsulated vaccines elicited high antibody levels which persisted for several months. The antibody levels were similar or superior to those elicited by conventional formulations of AIPO4-adsorbed TT or soluble Hib-T conjugate vaccine.

Adjuvants, Immunologic↗
PubMed1997

Localization of protein kinase C alpha and zeta during the decidualization in pseudopregnant rats.

Our previous data showed that at least five PKC isoforms (alpha, delta, zeta, lambda and tau) were present in the decidualization. In this study, we then localized the PKC alpha and zeta by immunohistochemistry in the decidualized uterine tissues. The decidualized uterine tissues were induced by trauma-stimulation and fixed in formalin. The immunofluorescence were photographed by confocal microscope. The data revealed that the fluorescence of PKC alpha was present in the deciduomata and myometrium. In the deciduomata, PKC alpha was mainly located in the surrounding nuclear. This phenomenon of localization was especially performed on day 2 and 3 of the decidualization, just on the time of higher frequence of cell mitosis. Since the myometrium with hypertrophy did not display the phenomenon of perinuclear localization, these suggested that the expression and localization of PKC alpha may be associated with the cell proliferation. On the other hand, the PKC zeta was also present and distributed broadly in the deciduomata and myometrium. This expression was increased and similar to the previous Western blot studies. Thus, the data confirmed that the various expression and localization of PKC isoforms may be correlated with the development of deciduomata.

Animals↗