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Biomedical subjects

A C Chang

Publications and source records attributed to A C Chang.

At least 127 records · Page 7Linked to original sources
PubMed1993

Expression of merosin in the thymus and its interaction with thymocytes.

Merosin is a 700 kDa multichain protein that has several properties in common with laminin, one of the major extracellular matrix proteins present in basement membranes. Both contain B1 and B2 light chains, but merosin has a distinct M-chain compared with the laminin A-chain. Merosin is present in the basement membrane of placenta, striated muscle, and peripheral nerve. Using the RT-PCR assay, we demonstrate that merosin, but not laminin, is also expressed in the thymus. A partial cDNA sequence of the mouse merosin M-chain was 88% identical to the human M-chain, and the deduced amino acid sequences were 95% identical. 18-24% of adult mouse thymocytes bound to human merosin in vitro. Mg2+, but not Ca2+, was essential for binding. Binding was inhibited by antibodies recognizing VLA alpha 6 or beta 1, suggesting that the VLA-6 integrin is a merosin receptor. An anti-beta 4 integrin subunit mAb failed to inhibit binding, suggesting that the alpha 6 beta 4 integrin was not involved. Thymocytes were fractionated into immature and mature populations based on their expression of the heat stable antigen, recognized by the J11d mAb. Virtually all thymocytes expressed VLA-6, but only immature thymocytes (J11d+) bound to meroson. PMA treatment did not significantly increase the binding of J11d+ thymocytes nor did induce binding in the mature J11d- population. In constrast, both splenic T cells and unseparated lymph node cells showed enhanced binding to merosin after PMA stimulation. The expression of merosin in the thymus and its selective interaction with immature thymocytes suggest that thymocyte-merosin interactions may play a role in T cell development.

Amino Acid Sequence↗
PubMed1993

Semiquantitative assessment of mitral regurgitation by Doppler color flow imaging in patients aged < 20 years.

Doppler color flow imaging is a rapid, noninvasive method to estimate the severity of mitral regurgitation (MR) in adult patients; theoretically, it should be possible to use the technique at least as successfully in infants and children, because problems with beam penetration should be diminished. Doppler color flow studies in 27 pediatric patients (age range 12 days to 17 years, median 7 months) with various degrees of MR (but without coexistent aortic regurgitation or intracardiac shunt) were analyzed. All patients underwent left ventriculography within 2 weeks of their color Doppler examination. Three sets of parameters were investigated, including: (1) maximal length of regurgitant jet: by itself, and indexed to cube root of body surface area (BSA) and to left atrial depth; (2) proximal width of jet; by itself, and indexed to cube root of BSA and to diameter of mitral annulus; and (3) regurgitant jet area (RJA): by itself, and indexed to BSA and left atrial area (LAA). Of these parameters, RJA indexed to BSA, and the ratio of RJA/LAA had the best correlation with angiographic grading (r = 0.84 and 0.92, respectively). With our instrumentation, the "cutoff" values in infants and children separating mild, moderate and severe MR appear to be 4 and 10 cm2/m2 for RJA/BSA, and 30 and 50% for RJA/LAA, respectively. Both inter- and intraobserver correlations were good for RJA (r = 0.95 and 0.94, respectively), and the ratio of RJA/LAA (r = 0.92 and 0.94, respectively). Semiquantitative assessment of MR appears to be possible in pediatric patients, using 1 instrument and a standardized technique.

Adolescent↗
PubMed1993

Multiple changes in VLA protein glycosylation, expression, and function occur during mouse T cell ontogeny.

VLA molecules (beta 1 integrins) are cell-surface alpha beta heterodimers that bind to extracellular matrix (ECM) proteins such as fibronectin, laminin, and collagen. We analyzed the expression, structure, and function of VLAs on mouse thymocytes, as a first step toward understanding their role in T cell development. Two major forms of beta 1 were detected, which differed in their extent of N-glycosylation and sialylation. No evidence for alternative splicing of beta 1 mRNA was obtained by PCR analyses. The larger (135 kDa, nonreduced) more basic beta 1 was the only form on nonmature (J11d+) adult thymocytes, with 135 kDa and larger beta 1-chains expressed on fetal thymocytes from day 14 of gestation through birth. The smaller (120 kDa, nonreduced), more acidic beta-chain was found exclusively on mature (J11d-) thymocytes and peripheral lymphocytes. VLA alpha-chain expression was also analyzed. Virtually all thymocytes were VLA-alpha 4+, -alpha 6+. VLA-alpha 5 was detected in both J11d+ and J11d- thymocytes by immunoprecipitation, but could not be analyzed in detail because of the lack of an appropriate mAb for flow cytometry. VLA-alpha 1 and -alpha 2 were immunoprecipitated only from cells within the J11d- population. Only J11d+ thymocytes (12 to 15%) bound to fibronectin (via VLA-4 and VLA-5) and binding to laminin (via VLA-6) was two to fourfold higher in J11d+ compared with J11d- thymocytes (60 to 80% vs 20 to 30%). The high percentage of J11d+ thymocytes adhering to laminin suggests that VLA-6 exists in an activated state on most thymocytes, in contrast to resting peripheral T cells. These data show that major changes in VLA glycosylation, expression, and ECM-binding capacity occur as thymocytes mature, supporting the hypothesis that VLA-ECM interactions play a role in T cell ontogeny.

Animals↗
PubMed1993

Real-time gas-exchange measurement of oxygen consumption in neonates and infants after cardiac surgery.

OBJECTIVES: The purposes of this study were: a) to measure oxygen consumption (VO2) in ventilated neonates and infants after cardiac surgery, utilizing a real-time gas exchange system; and b) to assess this new method by comparing the measured VO2 with calculated VO2 (using the Fick equation and simultaneously determined thermodilution cardiac output, measured hemoglobin, and measured mixed venous and arterial saturations). DESIGN: Prospective, comparison study. Comparison of measured VO2 and calculated VO2 using correlation coefficient, linear regression analysis, and bias and precision. SETTING: Cardiac intensive care unit in a children's hospital. PATIENTS: A total of 60 direct comparisons were made between measured and calculated VO2 in 15 patients (ages ranging from 4 days to 14.1 months with median age of 2.4 months) who were receiving mechanical ventilation after undergoing corrective cardiac surgery. INTERVENTIONS: a) Direct measurement of VO2 using gas exchange method involving a pneumotachograph and a gas sampling system; b) determination of cardiac output by the thermodilution technique; c) measurement of arterial and mixed venous oxygen content by blood sampling. MEASUREMENTS AND RESULTS: The absolute measured VO2 ranged from 19 to 154 mL/min with a mean of 52 +/- 32 mL/min (when indexed, the range was 81 to 367 mL/min/m2 with mean 185 +/- 69 mL/min/m2, or range 4.7 to 18.8 mL/min/kg with mean 10.4 +/- 3.3 mL/min/kg). While 34 (57%) of 60 measured VO2 values were within 10% of their respective calculated VO2 values, 58 (97%) of 60 were within 25%; the mean percent difference between measured and calculated VO2 values was 10.6 +/- 7.7%. In comparing the measured VO2 and calculated VO2, the correlation coefficient was good (r2 = .87; p < .01) and the linear regression equation was: measured VO2 = 1.1 x calculated VO2 -9.0 mL/min/m2. The mean difference, or bias, was 0 mL/min/m2 with precision of 26 and 52 mL/min/m2 (at 1 and 2 SD). As an alternative means of examining the measured VO2 data, we also directly compared the thermodilution cardiac output with cardiac output derived by using the measured VO2 and the Fick equation. The range of Fick-derived cardiac output was between 1.69 to 8.11 L/min/m2 (mean 3.72 +/- 1.56) and the range of thermodilution cardiac output was between 1.75 to 7.42 L/min/m2 (mean 3.71 +/- 1.36). The correlation coefficient between thermodilution cardiac output and Fick-derived cardiac output was good with r2 = .88 (p < .01) and the linear regression equation was: thermodilution cardiac output = 0.81 x Fick-derived cardiac output + 0.71 L/min/m2. The bias was -0.01 L/min/m2 with a precision of 0.54 L/min/m2 at 1 SD (or 1.08 L/min/m2 for 2 SD). CONCLUSIONS: Measured VO2 using a gas-exchange system compared favorably with calculated VO2 values using the Fick equation and simultaneously obtained thermodilution cardiac output and arterial and venous oxygen concentrations. By employing this breath-by-breath gas-exchange system, real-time VO2 measurement in ventilated neonates and infants is now feasible.

Bias↗
PubMed1993

Video-assisted thoracoscopic division of a vascular ring in an infant: a new operative technique.

We report the first successful use of thoracoscopy and video-assisted thoracic surgery (TVATS) techniques to relieve extrinsic tracheoesophageal compression produced by a vascular ring. The patient was a 3-month-old infant with postprandial regurgitation and a diagnosis of double aortic arch. After an uncomplicated operation and recovery, the infant was discharged on the second postoperative day. Refinement of technique and instrumentation may allow wider application of video-assisted thoracoscopic techniques in pediatric patients.

Aorta, Thoracic↗
PubMed1993

Incidental vesicoureteral reflux in neonates with antenatally detected hydronephrosis and other renal abnormalities.

Postnatal imaging findings were reviewed in 130 neonates and young infants referred for imaging evaluation of antenatally detected renal abnormalities. All children underwent voiding cystourethrography and upper urinary tract imaging with sonography and/or renal scintigraphy. Vesicoureteral reflux was present in 49 patients (38%) and was bilateral in 24. All grades of reflux were observed. Reflux occurred in 41 of 98 neonates (42%) in whom postnatal imaging revealed persistent upper tract abnormalities (eg, hydronephrosis, cysts, renal agenesis) and in eight of 32 (25%) with normal findings at postnatal sonography and/or renal scintigraphy. Reflux was the single most common urologic diagnosis and was the only postnatal abnormality in 12 patients (9%). The authors conclude that neonates with antenatally detected hydronephrosis should be routinely screened for reflux with voiding cystography. Detection and aggressive management of reflux in the asymptomatic neonate in whom renal growth and function are unimpaired theoretically offer the best opportunity for preventing renal injury later in childhood.

Female↗
PubMed1993

Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock.

This study was designed to test the hypothesis that tissue factor pathway inhibitor (TFPI) plays a significant role in vivo in regulating coagulation that results from exposure of blood to tissue factor after vascular injury as in the case of gram negative sepsis. Highly purified recombinant TFPI (6 mg/kg) was administered either 30 min or 4 h after the start of a lethal intravenous Escherichia coli infusion in baboons. Early posttreatment of TFPI resulted in (a) permanent seven-day survivors (5/5) with significant improvement in quality of life, while the mean survival time for the controls (5/5) was 39.9 h (no survivors); and (b) significant attenuations of the coagulation response and various measures of cell injury, with significant reductions in pathology observed in E. coli sepsis target organs, including kidneys, adrenals, and lungs. TFPI administration did not affect the reduction in mean systemic arterial pressure, the increases in respiration and heart rate, or temperature changes associated with the bacterial infusion. TFPI treated E. coli infected baboons had significantly lower IL-6 levels than their phosphate buffered saline-treated controls, however tumor necrosis factor levels were similarly elevated in both groups. In contrast to the earlier 30-min treatment, the administration of TFPI at 4 h, i.e., 240 min, after the start of bacterial infusion resulted in prolongation of survival time, with 40% survival rate (2/5) and some attenuation of the coagulopathic response, especially in animals in which fibrinogen levels were above 10% of normal at the time of TFPI administration. Results provide evidence for the significance of tissue factor and tissue factor pathway inhibitor in bacterial sepsis, and suggest a role for blood coagulation in the regulation of the inflammatory response.

Animals↗
PubMed1993

Early bidirectional cavopulmonary shunt in young infants. Postoperative course and early results.

BACKGROUND: Despite the recent wide applicability of the bidirectional cavopulmonary shunt, there is limited reported experience in performing these shunts in infants 6 months or younger. METHODS AND RESULTS: Before October 1992, 17 consecutive infants aged 4.2 to 6.5 months (median, 6.1 months) underwent bidirectional cavopulmonary shunts. The diagnoses were hypoplastic left heart syndrome (n = 7), single right ventricle (n = 5), and single left ventricle (n = 5). All but 2 patients had prior palliative surgery. The bidirectional cavopulmonary shunt was performed early on an elective basis in 9 patients; the remaining patients had progressive cyanosis (6 patients), severe ventricular failure (1 patient), and coexisting restrictive bulboventricular foramen (1 patient). The median preoperative pulmonary arterial pressure and pulmonary vascular resistance were 15 mm Hg and 2.3 U.m2, respectively. One patient died; the overall hospital survival was 94%. The most common postoperative problem was transient systemic hypertension, observed in 14 (88%) of 16 survivors. Systemic arterial oxygen saturation increased from a median of 75% before surgery to a median of 85% after surgery (P < .05). The median hospital stay was 6 days. There were no late deaths during follow-up (median, 12.4 months). At postoperative cardiac catheterization performed in 9 of 16 survivors, there was no evidence of severe hypoxemia, shunt narrowing, or pulmonary arteriovenous fistulas. Of the 16 survivors, 6 have had a subsequent Fontan operation at a median age of 1.9 years; there were 5 survivors. CONCLUSIONS: Early bidirectional cavopulmonary shunt in young infants has shown encouraging early results and provides improved oxygenation with low morbidity and mortality. We speculate that an early bidirectional cavopulmonary shunt on an elective basis may reduce the deleterious sequelae of chronic hypoxemia, long-term ventricular volume overload, and repeated palliative procedures, thus yielding a more suitable Fontan candidate.

Arteriovenous Shunt, Surgical↗
PubMed1993

Embryonic cerebellar graft development during acute phase of gliosis in the cerebellum of pcd mutant mice.

Anatomical and biochemical changes in cerebellum after the onset of pcd gene defects have revealed in addition to Purkinje cell degeneration, the occurrence of secondary degenerative events in granule neurons, neurons of the inferior olivary complex and deep cerebellar nuclei. Transplantation in young mutant animals thereby presents a prospect that not only the missing Purkinje cells may be replaced but the subsequent transneuronal losses may be minimized. The present study has evaluated the outcome of implanting embryonic cerebellar cell suspensions into pcd mutants at the age of 45 day-old, a stage marked by the end of Purkinje cell degeneration. Immunocytochemistry (ICC) was used to monitor the extent of gliosis in host cerebellum and to trace the development of embryonic Purkinje cells grafted. The results suggest that the donor cells have no apparent difficulty in survival during reactive gliosis. Migration of these neuroblasts from the grafted zone into adjacent host molecular layer and significant expression of calcium binding protein (CaBP) by grafted Purkinje cells were noted within 9 days after transplantation. Dendritic patterns of grafted Purkinje cells are well-developed by day 17 post transplantation up to 3 months. In addition, synaptic contacts between host fiber endings and the CaBP-positive dendritic spines are present in the molecular layer of folia containing the graft, suggesting synaptic integration between graft and host.

Acute Disease↗
PubMed1993

Molecular characterization of a murine homologue of alpha 2C4 adrenoceptor subtype gene.

A clone MA2C4 encoding the murine homologue of adrenoceptor alpha 2C4 was identified, amplified and purified from a mouse genomic library (EMBL-3). The Pstl-EcoRl digested fragment (2409 base pairs) of the clone contains the nucleotide sequence encoding a putative receptor protein (458 amino acids), which is highly homologous in the transmembrane and G protein-coupling domains to the human and rat isoceptors. The 5' untranslated region (0.4kb) is characterized by high GC content and CpG island count whereas a polyadenylation signal (AATAAA) is located 481 base pairs downstream from the termination codon in the 3' untranslated region (0.6kb).

Amino Acid Sequence↗
PubMed1992

Molecular cloning and characterization of a mouse alpha 2C2 adrenoceptor subtype gene.

A clone MA2C2 encoding the murine homologue of adrenoceptor alpha 2C2 was isolated from a mouse genomic library using a subtype specific probe. The nucleotide and the deduced amino acid sequences derived from an ApaI fragment (2 kb) of the clone reveal a single open reading frame encoding a putative receptor protein of 455 amino acids. The 5' untranslated region (0.5 kb) sequenced is characterized by high GC content and CpG island count.

Amino Acid Sequence↗
PubMed1992

Reactions of thrombin-serpin complexes with thrombospondin.

Activated platelets release proteins that form stable complexes with thrombin (J. J. Miller, P. C. Browne, and T. C. Detwiler, Biochem. Biophys. Res. Commun. 151, 9-15, 1988). A working model for the reaction (P. C. Browne, J. J. Miller, and T. C. Detwiler, Arch. Biochem. Biophys. 265, 534-538, 1988) includes a dissociable complex of thrombin with released platelet protease nexin, leading to formation of a nondissociable thrombin-nexin complex that then becomes disulfide linked to thrombospondin. This disulfide-linked complex is converted back to the thrombin-nexin complex by reduction of disulfide bonds. Results that allow elaboration on this model are presented. After longer periods of incubation or after incubation with higher concentrations of thrombin, the amount of thrombin complexed with thrombospondin exceeded the amount of thrombin-nexin complex recovered after reduction of disulfide bonds. When the reaction mixture included inhibitors of formation of the thrombin-nexin complex, a slow formation of the thrombin-thrombospondin complex was observed. It was concluded that there is a nexin-independent as well as the faster nexin-dependent disulfide linkage of thrombin to thrombospondin. Addition of thrombin-antithrombin III complexes to the supernatant solution of activated platelets also led to complexes with thrombospondin, demonstrating that serpins other than platelet protease nexin facilitate incorporation of thrombin into complexes with thrombospondin. By heparin affinity chromatography, it was shown that thrombin-nexin complexes dissociably associate with thrombospondin prior to formation of disulfide-linked complexes. These observations are incorporated into a more detailed model of the reaction.

Blood Platelets↗
PubMed1992

Characterization of a glial associated antigen GA-1 by monoclonal antibody.

A glial antigen (GA-1) was identified by monoclonal antibodies (MAb) raised against C6 rat glioma cells. MAb-7D3 (IgG2a kappa) revealed GA-1 as a single protein band with a Rf value of 0.09 by the use of basic-PAGE Western blot. SDS-PAGE Western blot and radioimmunoprecipitation (RIP) further resolved GA-1 into two subunits with a molecular weight of 200 and 78 kDa respectively. Subcellular localization by immunocytochemical staining revealed its cytosolic presence with a punctate pattern perinuclearly. Significant expression of GA-1 may be detected in 4 glioma or glial cell lines derived from rat brain. However, no expression may be detected in the rest of the 18 mammalian cell lines or primary neural cell cultures examined. All of the above data thereby suggest that GA-1 may be glial specific whereas the epitope of GA-1 defined by MAb-7D3 is species (rat) specific.

Animals↗
PubMed1992

Anticoagulant and fibrinolytic activities are promoted, not retarded, in vivo after thrombin generation in the presence of a monoclonal antibody that inhibits activation of protein C.

This study examines the assumption that both the anticoagulant and fibrinolytic activity that follow the generation of thrombin induced by infusion of factor Xa/PCPS are due to generation of activated protein C. Untreated controls or animals given unrelated antibody were compared with animals pretreated with a specific monoclonal antibody to protein C (HPC4). Compared with untreated controls excess HPC4 substantially reduced the level of protein C activation as observed by protein C immunoblotting and enzyme-linked immunosorbent assay for antitrypsin/activated protein C complexes. Despite this, the anticoagulant activity as reflected by the decline of factors Va and VIIIa levels (as observed by coagulation assays and by factor V immunoblotting) was significantly greater than controls. The fibrinolytic activity (as observed by assays of tissue plasminogen activator, D-Dimer, alpha 2-antiplasmin) also was significantly greater than controls. We conclude that neutralization of the protein C anticoagulant system while resulting in a significantly more intense coagulant response to Xa/PCPS does not preclude inactivation of factors Va and VIIIa and the full expression of the fibrinolytic response. We conclude further that after thrombin generation in vivo, protein C activation is not a prerequisite for the promotion of the fibrinolytic response previously observed, and that the inactivation of factors Va/VIIIa may be mediated by enzymes other than activated protein C. The reduction in alpha 2-antiplasmin levels in association with increased tissue plasminogen activator activity suggests that plasmin is a likely candidate.

Animals↗
PubMed1992

Role of peptido-leukotrienes in the genesis of early ventricular arrhythmias during acute myocardial ischaemia in rats.

Changes in cardiac ventricular concentrations of peptidoleukotrienes (peptido-LTs) following coronary artery ligation and the effects of lipoxygenase inhibition and leukotriene antagonism on the cardiovascular responses to acute myocardial ischaemia were studied in pentobarbitone-anaesthetised rats. It was found that the left ventricular peptido-LT levels significantly increased at 2.5 and 5 min after left coronary artery ligation while the changes in right ventricle were not statistically significant. Pretreatment with nordihydroguaiaretic acid 25, 50 or 100 mg/kg caused marked depletion of ventricular peptido-LT content, but did not significantly prevent the blood pressure or heart rate changes, the occurrence of ventricular tachycardia or fibrillation, or the mortality of the animals following coronary artery ligation. Administration of SK&F 102922, even at doses which caused marked decreases in blood pressure and heart rate, also did not significantly alter the cardiovascular changes and the mortality rate induced by left coronary artery ligation. It is, therefore, suggested that the occurrence of ventricular arrhythmias and haemodynamic changes during the early phase of acute myocardial ischaemia may not be due to the augmented synthesis of peptido-LTs in cardiac tissue.

Acute Disease↗
PubMed1992

Outcome and assessment after the modified Fontan procedure for hypoplastic left heart syndrome.

BACKGROUND: We reviewed the outcome of 76 consecutive patients (age range, 5 months to 6 years; median age, 19 months) who underwent a modified Fontan procedure after initial palliative surgery for hypoplastic left heart syndrome (HLHS) between January 1984 and December 1989. METHODS AND RESULTS: Modifications of the Fontan procedure included transatrial baffle of pulmonary venous return to the tricuspid valve (n = 10) or inferior vena cava baffle within the right atrium to the superior vena caval-pulmonary artery anastomosis, with pulmonary artery augmentation (n = 66). Actuarial survival rates were 74% (1 month), 58% (12 months), 56% (2 years), and 52% (4 years). Of the 43 survivors, 25 patients have returned for postoperative cardiac catheterization at a medium of 13 months after the Fontan procedure. Mean +/- SD hemodynamic values were cardiac index, 2.8 +/- 0.6 l/min/m2; right arterial pressure, 11 +/- 2 mm Hg; pulmonary artery wedge pressure, 6 +/- 3 mm Hg; and arterial oxygen saturation, 94 +/- 3%. No patient had significant tricuspid or native pulmonary valve insufficiency. CONCLUSIONS: Survival after the Fontan procedure in patients with HLHS is comparable to survival after a Fontan procedure in patients with other complex congenital heart lesions. In the subgroup of patients with HLHS who survived both reconstructive surgery and a Fontan procedure and have been evaluated by cardiac catheterization after a Fontan procedure, the use of the right ventricle as the systemic ventricle yielded excellent intermediate results for Fontan physiology.

Cardiac Catheterization↗