Search PubMed⌕ Search

Biomedical subjects

A Chang

Publications and source records attributed to A Chang.

At least 217 records · Page 12Linked to original sources
PubMed1991

Catalytic triad residue mutation (Asp156----Gly) causing familial lipoprotein lipase deficiency. Co-inheritance with a nonsense mutation (Ser447----Ter) in a Turkish family.

We studied the molecular basis of familial Type I hyperlipoproteinemia in two brothers of Turkish descent who had normal plasma apolipoprotein C-II levels and undetectable plasma post-heparin lipoprotein lipase (LPL) activity. We cloned the cDNAs of LPL mRNA from adipose tissue biopsies obtained from these individuals by the polymerase chain reaction and directional cloning into M13 vectors. Direct sequencing of pools of greater than 2000 cDNA clones indicates that their LPL mRNA contains two mutations: a missense mutation changing codon 156 from GAU to GGU predicting an Asp156----Gly substitution and a nonsense mutation changing the codon for Ser447 from UCA to UGA, a stop codon, predicting a truncated LPL protein that contains 446 instead of 448 amino acid residues. Both patients were homozygous for both mutations. Analysis of genomic DNAs of the patients and their family members by the polymerase chain reaction, restriction enzyme digestion (the GAT----GGT mutation abolishes a TaqI restriction site), and allele-specific oligonucleotide hybridization confirms that the patients were homozygous for these mutations at the chromosomal level, and the clinically unaffected parents and sibling were true obligate heterozygotes for both mutations. In order to examine the functional significance of the mutations in this family, we expressed wild type and mutant LPLs in vitro using a eukaryotic expression vector. Five types of LPL proteins were produced in COS cells by transient transfection: (i) wild type LPL, (ii) Asp156----Gly mutant, (iii) Ser447----Ter mutant, (iv) Gly448----Ter mutant, and (v) Asp156----Gly/Ser447----Ter double mutant. Both LPL immunoreactive mass and enzyme activity were determined in the culture media and intracellularly. Immunoreactive LPLs were produced in all cases. The mutant LPLs, Asp156----Gly and Asp156----Gly/Ser447----Ter, were devoid of enzyme activity, indicating that the Asp156----Gly mutation is the underlying defect for the LPL deficiency in the two patients. The two mutant LPLs missing a single residue (Gly448) or a dipeptide (Ser447-Gly448) from its carboxyl terminus had normal enzyme activity. Thus, despite its conservation among all mammalian LPLs examined to date, the carboxyl terminus of LPL is not essential for enzyme activity. We further screened 224 unrelated normal Caucasians for the Ser447----Ter mutation and found 36 individuals who were heterozygous and one individual who was homozygous for this mutation, indicating that it is a sequence polymorphism of no functional significance. Human LPL shows high homology to hepatic triglyceride lipase and pancreatic lipase.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗
PubMed1991

C4b-binding protein exacerbates the host response to Escherichia coli.

Activated protein C is a plasma anticoagulant. For activated protein C to function as an anticoagulant, it must form a complex with protein S. Protein S anticoagulant activity is neutralized by formation of a reversible complex with C4b binding protein (C4bBP). C4bBP is an acute-phase plasma protein. When C4bBP levels increase, mass action forces the level of free protein S to decrease, giving rise to an acquired functional protein S deficiency. It has been proposed that these elevated C4bBP levels and the resultant acquired deficiency of protein S that occurs in inflammation could contribute to a hypercoagulable state. An experimental model to test this hypothesis was suggested by our previous studies that demonstrated that inhibition of protein C activation rendered baboons hypercoagulable in response to sublethal Escherichia coli infusion (J Clin Invest 79:918, 1987). We have extended these studies to examine the effect of inhibition of protein S activity with C4bBP in the host (baboon) response to infusion of sublethal concentrations of E coli organisms. Five sets of animals were studied: (1) those challenged with sublethal concentrations of E coli alone (0.4 x 10(10)/kg); (2) those supplemented only with C4bBP (20 mg/kg); (3) those challenged with the same level of E coli but supplemented with C4bBP (20 mg/kg); (4) those challenged with sublethal E coli and supplemented with C4bBP (20 mg/kg) and sufficient protein S (2.3 mg/kg) to fill the protein S binding sites on C4bBP; and (5) those challenged with lethal concentrations of E coli. Sublethal E coli infusion (group 1 animals) caused only an acute-phase response with no consumption of fibrinogen, detectable organ damage, or detectable tumor necrosis factor (TNF) in the plasma. C4bBP infusion (group 2 animals) resulted in no significant physiologic changes, no detectable plasma TNF, and little change in fibrinogen level. The group 3 animals, receiving both sublethal E coli and C4bBP, exhibited rapid consumption of fibrinogen, systemic organ damage, and detectable circulating TNF ultimately leading to death. The overall response of this group was very similar to the response of the group 5 animals receiving an LD100 dose of E coli. The group 4 animals, which were treated exactly as above except that C4bBP was supplemented with a slight excess of protein S, responded essentially like those that received sublethal E coli alone. These studies suggest that the elevation of C4bBP during an inflammatory response can contribute to fibrinogen consumption and vascular damage. This vascular damage may be associated with enhanced elaboration of cytokines like TNF.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Correlates of diurnal sleep patterns in infants of adolescent and adult single mothers.

Sleep behavior has been related to both child and environmental factors, but the relative importance of these factors is not yet clear. This study was an examination of the relation of diurnal sleep patterns to perinatal risk, infant temperament, home environment, parenting stress, emotional support, and social class. Twenty-three adolescent and 23 single adult mothers and infants were assessed in the home at 4 and 12 months. Percent sleep during the night was most strongly related to parenting stress and variability of night sleep to emotional support. Emotional support mediated effects of stress at 4 months. Results support the value of clinical assessment of sleep behavior.

Adaptation, Psychological↗
PubMed1991

The effect of topical retinoids on the leukotriene-B4-induced migration of polymorphonuclear leukocytes into human skin.

Systemic retinoids are effective in a variety of inflammatory dermatoses. Disorders in which polymorphonuclear leukocytes (PMN) are involved, such as psoriasis and acne, respond particularly well to various retinoids. However, side-effects restrict the use of systemic retinoids to severe manifestations. Topical application might provide the possibility of avoiding the systemic side-effects of these compounds. In this communication we report on the modulation of transepidermal migration of PMN by topical application of all-trans-retinoic acid, 13-cis-retinoic acid, arotinoid methyl sulphone and arotinoid ethyl sulphone. Test areas of healthy volunteers were pretreated with these retinoids in a cream base and with corresponding placebo creams, and intraepidermal accumulation of PMN was quantified 24 h after epicutaneous challenge with leukotriene B4 (LTB4), using elastase as a marker enzyme. Topical treatment with 13-cis-retinoic acid resulted in a marked and statistically significant inhibition of the LTB4-induced migration of PMN. All-trans-retinoic acid, arotinoid methyl sulphone and arotinoid ethyl sulphone reduced the accumulation of PMN slightly, but not statistically significantly. Topical treatment with arotinoid methyl sulphone had no effect.

Administration, Topical↗
PubMed1991

Maturation of the yeast plasma membrane [H+]ATPase involves phosphorylation during intracellular transport.

In this study we show that the plasma membrane [H+]ATPase of Saccharomyces cerevisiae is phosphorylated on multiple Ser and Thr residues in vivo. Phosphorylation occurs during the movement of newly synthesized ATPase from the ER to the cell surface, as revealed by the analysis of temperature-sensitive sec mutants blocked at successive steps of the secretory pathway. Two-dimensional phosphopeptide analysis of the ATPase indicates that, although most sites are phosphorylated at or before arrival in secretory vesicles, some phosphopeptides are unique to the plasma membrane. Phosphorylation of plasma membrane-specific site(s) is associated with increased ATPase activity during growth on glucose. Upon glucose starvation, dephosphorylation occurs concomitantly with a decrease in enzymatic activity, and both are rapidly reversed (within 2 min) upon readdition of glucose. We suggest that reversible, site-specific phosphorylation serves to adjust ATPase activity in response to nutritional signals.

Biological Transport↗
PubMed1991

Ten-year experience with cyclosporine as primary immunosuppression in recipients of renal allografts.

Cyclosporine has been used as primary immunosuppression in renal allograft recipients in our unit for the past decade. The overall clinical experience and long-term effects of the agent are reviewed. There were 461 consecutive recipients of kidney grafts; 379 received grafts from cadaver donors (CAD) and 82 from living related donors (LRD). Four separate clinical protocols were used sequentially using progressively decreasing doses of CyA; azathioprine was added in group 4 recipients of LRD grafts, and in patients receiving secondary CAD grafts (group 5). The patient mortality rate was less than 5%, with sepsis being the prime contributor. The majority of kidney grafts were lost within the first 2 months after operation; those that never functioned were found almost invariably to have been irreversibly rejected. During the subsequent years of follow-up, attrition of CAD grafts was significantly greater than LRD grafts. In contrast, the attrition rate of primary and secondary CAD grafts was the same after the first 3 months, emphasizing the importance of early immunologic graft destruction. Primary nonfunction occurred in 49% of CAD kidneys and 17% of LRD grafts; however 71% of initially nonfunctioning LRD grafts never functioned at all compared to 34% of CAD grafts, the majority of such organs undergoing fulminate rejection. Individual graft loss after 1 year was almost inevitably due to chronic rejection; there were no differences in long-term allograft function among the treatment groups. Although CyA has improved overall results of kidney transplantation, chronic rejection remains a major unresolved problem.

Adult↗
PubMed1991

Puerperal haematomas.

Forty-seven out of 31,628 patients delivered in our hospital over the past 5 years developed puerperal genital tract haematomas. Four cases, representing different types of haematoma which required different managements, were presented to illustrate this problem. A literature review was also made.

Adult↗
PubMed1991

The role of vasopressin and atrial natriuretic factor in postoperative fluid retention after the Fontan procedure.

The Fontan procedure results in right atrial distention and is complicated by fluid retention. Since systemic fluid balance may be hormonally mediated in part and related to right atrium size, we measured plasma atrial natriuretic factor and plasma arginine vasopressin levels in 19 patients undergoing the Fontan procedure and in 12 control patients undergoing other types of heart operations. Preoperative plasma atrial natriuretic factor levels were higher in patients undergoing the Fontan procedure than in control patients (95 +/- 16 pg/ml preoperatively versus 50 +/- 8 pg/ml; p less than 0.05) and increased in patients undergoing the Fontan procedure to 330 +/- 48 pg/ml by postoperative day 2 (p less than 0.05) but not in control patients. Increased plasma atrial natriuretic factor levels could enhance capillary transudation, but elevated plasma atrial natriuretic factor levels should also enhance diuresis and prevent fluid retention. Vasopressin levels, however, were also increased in patients undergoing the Fontan procedure (from 9 +/- 2 pg/ml preoperatively to 144 +/- 37 pg/ml at end of operation) and were higher and remained elevated longer than in control patients undergoing heart operations (37 +/- 7, 20 +/- 4, 16 +/- 6 pg/ml on postoperative days 1, 2, and 3 to 10 for the Fontan group compared with 15 +/- 4, 4 +/- 1, 4 +/- 2 pg/ml for control patients). Vasopressin levels were highest in the Fontan group with the most severe fluid retention and effusions (for example, 51 +/- 10 pg/ml versus 23 +/- 4 pg/ml, on postoperative day 1). Increased vasopressin and atrial natriuretic factor could act synergistically to result in the development of effusions after the Fontan procedure when atrial natriuretic factor-induced capillary transudation is combined with vasopressin-induced antidiuresis.

Atrial Natriuretic Factor↗
PubMed1991

Child care options for ill children.

Care of ill children who normally attend out-of-home child care programs poses a problem for many working parents, employers, and child care workers. Children cared for in child care centers have an increased incidence of illness and consequently their parents miss work more often compared with children cared for in other child care arrangements. Programs for the care of ill children are discussed to provide the practicing pediatrician with an understanding of the various programs currently or potentially available in the community. The paper ends with a discussion of the various solutions to enhance the economic gains of working parents while serving the need of children for nurturant care.

Child Care↗
PubMed1991

Rifampin and ansamycin interactions with cyclosporine after renal transplantation.

Cyclosporine whole blood concentrations are routinely monitored to help ensure optimal therapy. Several drugs have been shown to alter cyclosporine disposition by altering hepatic metabolism. Rifampin, a potent enzyme inducer, has been demonstrated to increase cyclosporine clearance. The effects of ansamycin, a chemically related investigational antibiotic, on cyclosporine disposition, have not been previously published. We report a renal transplant patient receiving cyclosporine and consecutive therapy with rifampin and ansamycin. When compared to rifampin, ansamycin's effect on cyclosporine disposition appeared to be delayed and of less magnitude. Further characterization of this interaction is required. Until this issue is resolved, we would advise careful monitoring of cyclosporine blood levels in patients receiving either rifampin or ansamycin in concert with cyclosporine.

Anti-Bacterial Agents↗
PubMed1991

Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody.

Gram-negative bacteremia poses a major health problem, causing one-half of cases of lethal septic shock acquired during hospitalization. Bacterial lipopolysaccharide (LPS) and the inflammatory cytokines, tumor necrosis factor (TNF) and interleukin-1 (IL-1), have been shown to be essential mediators of septic shock. Among the effects of these mediators is a coagulopathy that may be triggered by induced expression of tissue factor (TF) on macrophages and endothelial cells. We now report that 500 micrograms/kg of either immunoglobulin G (IgG) or Fab fragments of a monoclonal antibody against TF administered to baboons as a pretreatment attenuates the coagulopathy and protects against LD100 Escherichia coli. This study provides direct evidence of an essential effector role for TF in septic shock.

Adrenal Glands↗
PubMed1990

A structural change in the Neurospora plasma membrane [H+]ATPase induced by N-ethylmaleimide.

The reaction of N-ethylmaleimide (NEM) with Cys-532 of the Neurospora plasma membrane [H+]ATPase results in inhibition of ATP hydrolysis which is protected by MgADP (Pardo, J. P., and Slayman, C. W. (1989) J. Biol. Chem. 264, 9373-9379). To examine the conformational state of the ATPase upon NEM modification, we have used limited trypsinolysis and domain-specific antibodies. The NEM-reacted ATPase shows increased sensitivity to trypsin, particularly in the central hydrophilic region of the polypeptide thought to contain the ATP binding and phosphorylation sites. In addition, competitive enzyme-linked immunosorbent assays indicate that the C-terminal domain of the ATPase becomes more accessible to antibody binding while the N-terminal region becomes more protected. The NEM-induced structural change is accompanied by loss of the ability to form a phosphoenzyme intermediate. The change in tertiary conformation occurs specifically upon NEM reaction with Cys-532 since neither NEM modification of Cys-545 nor fluorescein 5'-isothiocyanate modification of Lys-474 alters the tryptic digestion pattern of the ATPase. Furthermore, modification of Cys-532 with the less bulky sulfhydryl reagent methyl methanethiosulfonate does not result in a detectable structural change or loss of enzymatic activity. Thus, the introduction of a relatively bulky maleimide group at Cys-532 has specific and far-reaching effects upon the structure and function of the ATPase.

Adenosine Triphosphate↗
PubMed1990

Plasma membrane-stimulated vanadate-dependent NADH oxidation is not the primary mediator of vanadate toxicity in Saccharomyces cerevisiae.

Interactions of oxyvanadium compounds with cellular metabolism have recently been demonstrated. Membrane-stimulated vanadate-dependent NADH oxidation has been hypothesized to involve the cellular accumulation of H2O2, which may cause the vanadate sensitivity of animals and microbes. This report shows that the vanadate-dependent NADH oxidation activity of the yeast plasma membrane requires oxygen and is present in vanadate-resistant mutants of Saccharomyces cerevisiae. In addition, the vanadate sensitivity of growth in S. cerevisiae is the same during aerobic and anaerobic growth. These results imply that neither plasma membrane-mediated vanadate-stimulated NADH oxidation, nor any other oxidative process, is the primary cause of vanadate sensitivity in yeast cells.

Aerobiosis↗
PubMed1990

Participation in alternative care: relationship to anxiety, depression, and hostility.

Women's psychological mood and its relationship to satisfaction with participatory perinatal care was examined using a two-group evaluation design of convenience samples (N = 99). Women entered the perinatal experience with similar degrees of anxiety, depression and hostility, but contrary to prediction, the type of perinatal experience, conventional or alternative, was not associated with their psychological mood. However, women in both groups reported less anxiety 2 to 3 days and 4 weeks after delivery than they reported having in general prior to delivery. Women who were more satisfied with care and their participation in care, regardless of whether they had an alternative or conventional perinatal experience, reported less anxiety and depression immediately post delivery. In 4 weeks, satisfaction and participation in care were still negatively related to anxiety.

Adult↗
PubMed1990

Percutaneous intrathoracic aspiration biopsy.

An analysis of 617 percutaneous intrathoracic aspiration biopsies (PIAB) performed on 587 patients with pulmonary and mediastinal lesions between 1954 and 1985 are presented. The effectiveness of the procedure between 1954 and 1980 and between 1981 and 1985 with a positivity of 71.6% and 84.9%, respectively, was compared. These results are statistically significant and reflect improvement in the technique employed. A greater positivity was found where the lesion measured 2 to 3 cm in diameter. Complications for this series were 7.8%. In diffuse infiltrating lesions, the positivity is less than that obtained for the whole series, and the risk of developing a pneumothorax is greater. The false-negative cases include those in which an inadequate sample was obtained for diagnosis (13.9% of the total series) and samples containing elements of the chest wall or blood (5.2%).

Adolescent↗