Biomedical subjects

B L Baker

Publications and source records attributed to B L Baker.

At least 19 recordsLinked to original sources

PubMed2000

Dexamethasone inhibits insulin-like growth factor signaling and potentiates myoblast apoptosis.

In the critically ill, glucocorticoids induce myopathy, combining profound protein catabolism and mild myotubular death. Insulin-like growth factors (IGFs) inhibit muscle catabolism through activation of phosphatidylinositol 3-kinase (PI3K). Using rat L6 myoblasts, we show that IGF-I also acts through PI3K to inhibit apoptosis induced by hyperosmolar metabolic stress with 300 mM mannitol. We find that the glucocorticoid dexamethasone inhibits this antiapoptotic effect of IGF-I by impairing PI3K signaling. Dexamethasone induces overexpression of the PI3K subunit p85alpha, which, in turn, competes with the complete PI3K heterodimer for binding at insulin receptor substrate-1, inhibiting PI3K activation. Dexamethasone blocks IGF-I-induced phosphorylation of Akt, a PI3K-dependent process. Increased cellular p85alpha abundance, induced by either 10 microM dexamethasone or transient transfection with a plasmid coding for p85alpha, significantly inhibits IGF-I rescue from apoptosis induced by mannitol, as indicated by both loss of cell viability and increased activity of caspase-3 by fluorogenic assay. Conversely, constitutively active PI3K inhibits death induced by mannitol, even in the presence of dexamethasone. These findings may have particular relevance in the pathogenesis of acute steroid myopathy in critical illness, in which catabolic glucocorticoid effects combine with acute metabolic stressors, including sepsis, fasting, and chemical denervation.

Animals↗

PubMed2000

Applications of the expressed emotion construct to young children with externalizing behavior: stability and prediction over time.

We explored the utility of the Expressed Emotion (EE) construct with a community sample of young children (N = 91), studying the stability of EE scores over a 2-year period and the extent to which EE was associated with simultaneous and subsequent disruptive behavior. As part of a longitudinal study, families were assessed when the child was in preschool, 1st grade, and 3rd grade. Maternal EE was measured at preschool and 1st grade using the Five Minute Speech Sample and behavior ratings were obtained using the Child Behavior Checklist. At 3rd grade, the Diagnostic Interview Schedule for Children was used to determine DSM-IV diagnoses. The stability of the EE rating over the 2-year period from preschool to 1st grade was statistically significant although modest. At 1st grade, EE ratings were significantly related to the extent of externalizing behavior problems. Regression analyses that controlled for maternal stress levels determined that preschool EE ratings predicted classification of ADHD over 4 years later, at 3rd grade. The relationships between EE and child problem behavior were almost exclusively determined by the EE criticism dimension; the emotional overinvolvement dimension was not related to child behavior. The implications of these findings are discussed.

Attention Deficit Disorder with Hyperactivity↗

PubMed2000

Expressed emotion, parenting stress, and adjustment in mothers of young children with behavior problems.

Expressed Emotion (EE), a measure of the emotional climate of the family, predicts subsequent adjustment of adults with mental disorder (Leff & Vaughn, 1985). Despite the acknowledged importance of the family in childhood disorders, there have been relatively few studies of expressed emotion with adolescents and school-aged children and virtually none focused on preschoolers. The present study utilized the Five Minute Speech Sample (FMSS) to examine how Expressed Emotion relates concurrently and longitudinally to child problem status in a community sample of 112 preschool-aged children. At preschool, the proportion of high EE increased significantly across three child groups: Comparison (8.1%), Borderline Problem (15.8%), and High Problem (41.2%); however, preschool EE was not predictive of subsequent child status at 1st grade. Expanded FMSS codes. tapping positive affect and worry about the child, were also related to child problem group at preschool and were predictive of subsequent child status at 1st grade. Because parents' stress and adjustment were also highly related to child problem group status, we examined whether the FMSS codes were essentially a proxy for these or whether they explained unique variance. In two stepwise regressions on preschool child group status (divided by total problems and by externalizing problems), maternal stress was the only variable to enter. Also, in predicting to 1st grade externalizing child group status, only maternal stress entered. Discussion focused on the extension of the EE construct and other FMSS coding to young children, and the need to recognize that to some extent these variables may reflect maternal stress and adjustment.

Adult↗

PubMed1999

Acute saline infusion reduces alveolar-capillary membrane conductance and increases airflow obstruction in patients with left ventricular dysfunction.

BACKGROUND: Impaired alveolar-capillary membrane conductance is the major cause for the reduction in pulmonary diffusing capacity for carbon monoxide (DLCO) in heart failure. Whether this reduction is fixed, reflecting pulmonary microvascular damage, or is variable is unknown. The aim of this study was to assess whether DLCO and its subdivisions, alveolar-capillary membrane conductance (DM) and pulmonary capillary blood volume (Vc), were sensitive to changes in intravascular volume. In addition, we examined the effects of volume loading on airflow rates. METHODS AND RESULTS: Ten patients with left ventricular dysfunction (LVD) and 8 healthy volunteers were studied. DM and Vc were determined by the Roughton and Forster method. The forced expiratory volume in 1 second (FEV1), vital capacity, and peak expiratory flow rates (PEFR) were also recorded. In patients with LVD, infusion of 10 mL. kg-1 body wt of 0.9% saline acutely reduced DM (12.0+/-3.3 versus 10.4+/-3.5 mmol. min-1. kPa-1, P<0.005), FEV1 (2.3+/-0.4 versus 2.1+/-0.4 L, P<0.0005), and PEFR (446+/-55 versus 414+/-56 L. min-1, P<0.005). All pulmonary function tests had returned to baseline values 24 hours later. In normal subjects, saline infusion had no measurable effect on lung function. CONCLUSIONS: Acute intravascular volume expansion impairs alveolar-capillary membrane function and increases airflow obstruction in patients with LVD but not in normal subjects. Thus, the abnormalities of pulmonary diffusion in heart failure, which were believed to be fixed, also have a variable component that could be amenable to therapeutic intervention.

Aged↗

PubMed1999

Leaving or launching? Continuing family involvement with children and adolescents in placement.

Postplacement involvement and well-being of 53 families who had placed their child into a residential facility were studied. Parents were interviewed an average of 1, 2, and 3.5 years following placement. Visitation remained moderately high, with some type of visit reported at least monthly at Time 3 by 83% of families. Expressed attachment was high and stable, and most parents reported experiencing less guilt than at the time of placement. Parents were still thinking and talking about the child frequently. They were more likely, over time, to view the placement as permanent, and for about two thirds, the ideal placement was a residential facility. Virtually all parents reported family life to be better following placement, especially in recreation, social life, and relationships with their other children.

Adaptation, Psychological↗

PubMed1998

Carbonothioate phospholipids as substrate for a spectrophotometric assay of phospholipase A2.

A continuous spectrophotometric assay for phospholipase A2 (PLA2) was developed using novel carbonothioate phospholipids. These phospholipid analogues contain a carbonothioate bond in the place of the sn-2 ester of the natural substrates of phospholipase A2 and were synthesized in a one-pot two-step reaction. Phospholipase A2 from cobra venom (Naja naja atra) hydrolyzes carbonothioate phospholipids and liberates a free thiol, alkylmercaptan, which is reacted with 5,5'-dithiobis(2-nitrobenzoic acid) to yield a product that absorbs at 412 nm. The kinetic studies on PLA2 hydrolysis of carbonothioate phospholipids were carried out in pure phospholipid forms and in Triton X-100 mixed micelles. The hydrolysis of pure carbonothioate phospholipids exhibits an interfacial activation phenomenon. The hydrolysis of phospholipid in mixed Triton X-100 micelles follows classical Michaelis-Menten kinetics. In a mixed micellar system, the catalytic efficiency observed with this series of substrates is two orders of magnitude lower than that of the hydrolysis of the natural substrate dipalmitoyl phosphocholine. However, these substrates bind to the enzyme over 10 times tighter than does the natural substrate. Application of this carbonothioate assay to screen both reversible and irreversible enzyme inhibitors of phospholipase A2 is also demonstrated.

Elapid Venoms↗

PubMed1998

Structural characterization and optimization of antibody-selected phage library mimotopes of an antigen associated with autoimmune recurrent thrombosis.

The presence of high titers of anti-cardiolipin antibodies (ACA's) of autoimmune origin, which are known to bind to plasma beta2-glycoprotein I (aka apolipoprotein H), correlates clinically with autoimmune recurrent thrombosis. Soluble beta2-glycoprotein I binds to solid-phase ACA (immobilized on a surface plasmon resonance chip) with a Kd of 1.4 microM, but if the reactants are reversed and beta2-glycoprotein I is on the solid-phase support, then the Kd is 52 nM. This 27-fold difference in affinity reflects the avidity/entropic advantage obtained for an antibody binding to an antigen that is made multivalent because it is attached to a solid phase. A mimotope of this antigen, selected from a phage display peptide library screen with an ACA, has been shown to bind to solid-phase ACA as a phage, using surface plasmon resonance. This peptide is representative of the motif from 37 peptides obtained in a previously reported phage library screen with this ACA (1). A synthetic version of this peptide, referred to as P4, has the sequence: A1G2P3C4I5L6L7A8R9D10R11C12P13G14, and binds to its selecting antibody with a Kd of 42 nM. NMR data indicate that proline-13 is present in both cis and trans configurations, and that these two geometries dramatically affect the overall tertiary structure of the molecule. The peptide lacking this proline binds severalfold better to the ACA, consistent with at least one of these structures having low affinity for binding ACA. Replacement of the arginine-9 position with a proline decreases binding affinity to ACA 10-fold. Another phage library-selected peptide has a proline in position 9, but also has a leucine in position 5, instead of isoleucine. Since its affinity for ACA is nearly as good as that for peptide P4, the phage library screening must have selected for a non-beta-branched amino acid in this position to compensate for the adverse effects of the arginine-9 to proline-9 substitution. The solution structure of a modified version of the antibody-selected phage peptide P4 with the central proline was determined. This peptide has one turn comprised of Ala-Pro-Asp-Arg, with the proline peptide bond in the cis configuration, and another turn that contains the disulfide and adjacent residues. If the disulfide is replaced by a thioether, and the central proline by an alpha-methyl proline, in an attempt to make the peptide more biologically stable, there is little adverse effect on affinity for ACA. The thioether bond/turn is fairly well defined with a Calpha to Calpha separation of 4.9 +/- 0.8 A. The alpha-methyl proline adopts the trans configuration, and this central Ala-(alpha-methyl-Pro)-Asp-Arg turn adopts a distorted type I turn conformation with a probable i to i+3 hydrogen bond. Modeling studies suggest that the proline peptide bond configuration switched from cis to trans in the presence of the alpha-methyl group on proline because of steric hindrance with the beta-carbon of the preceding residue. Overall, this peptidomimetic molecule is structurally very similar to the peptide with natural amino acids, with an rmsd difference of only 1.37 A, when comparing backbone atoms.

Antibodies, Anticardiolipin↗

PubMed1998

Siblings of children with mental retardation living at home or in residential placement.

Severe retardation in a child surely has an effect on all family members. Studies of non-disabled siblings in these families have indicated both emotional risks and perceived benefits. Little is known about how out-of-home placement of the child with retardation affects the siblings. Adolescent siblings of children with retardation living at home (N = 25) or in residential placement (N = 20) were contrasted with siblings of children without retardation (N = 28), on measures obtained from their mothers and themselves. Despite their different situations, these siblings were highly similar on measures of psychological adjustment, self-esteem, and family environment. Sibling relationships, however, were less intense, with less warmth but also lower conflict, in families where the child lived out of the home. Most siblings of children with retardation reported positive personal growth experiences while also expressing realistic concerns about the future. Siblings of children with retardation had beliefs and attitudes about placement that were highly consistent with the child's current living situation.

Adolescent↗

PubMed1996

Preschool children with externalizing behaviors: experience of fathers and mothers.

Childhood behavior disorders are related to family stress and maladjustment. Little is known, however, about the adjustment of families with preschool-aged children at risk for subsequent behavior disorders. Moreover, fathers' perceptions of child problem behavior and their reactions to it generally have been neglected. Subjects were mothers and fathers of 52 preschool-aged children assigned to one of three groups: control, moderate externalizing, and high externalizing. Higher child externalizing behavior was associated with greater negative family impact, lowered parenting sense of efficacy, and child-rearing practices that were more authoritarian and less authoritative. Mothers and fathers did not differ in actual perceived level of child behavior problems, although both believed that mothers saw more problems. Child Group x Parent interactions indicated that mothers experienced increased stress and a need for help with moderate as well as high child externalizing behaviors, whereas fathers were not elevated on these measures unless the child's externalizing behaviors were high. Implications of these findings for early family intervention are considered.

Adaptation, Psychological↗

PubMed1996

Family involvement in residential treatment.

Social policy stresses the importance of the family's continuing involvement with members in residential placement. We studied involvement of families with 163 children and adults in residential treatment and with their programs. Parent and staff reports of family involvement showed high agreement. The average family had 21 contacts annually with the family members; these related only marginally to the extent of involvement with the residents' programs. There was no evidence of detachment, a lessening of involvement over time. Multiple regression found three variables that accounted for 52% of the variance in contacts: higher involvement related to less distance from the facility, greater expectations that the family member would return home, and lower levels of mental retardation. Implications of findings for increasing family involvement were discussed.

Adolescent↗

PubMed1995

Enhancement of Agkistrodon piscivorus piscivorus venom phospholipase A2 activity toward phosphatidylcholine vesicles by lysolecithin and palmitic acid: studies with fluorescent probes of membrane structure.

The activity of phospholipase A2 from snake venom to hydrolyze bilayers of phosphatidylcholines is greatly enhanced by the presence of the hydrolysis products, lysolecithin and fatty acid, in the bilayer. The fluorescence of several probes of membrane structure was used to monitor changes in bilayer physical properties during vesicle hydrolysis. These changes were compared to emission spectra and fluorescence polarization results occurring upon direct addition of lysolecithin and/or fatty acid to the bilayer. The excimer to monomer ratio of 1,3-bis(1-pyrene)propane was insensitive to vesicle hydrolysis, suggesting that changes in the order of the phospholipid chains were not relevant to the effect of the hydrolysis products on phospholipase activity. The fluorescence of 6-propionyl-2-(dimethylamino)-naphthalene (Prodan) suggested that the polarity of the bilayer in the region of the phospholipid head groups increases as the hydrolysis products accumulate in the bilayer. The fluorescence of 6-dodecanoyl-2-(dimethylamino)naphthalene (Laurdan) confirmed that such effects were restricted to the bilayer surface. Furthermore, the lysolecithin appeared to be the product most responsible for these changes. These results suggested that lysolecithin increases the activity of phospholipase A2 during vesicle hydrolysis by disrupting the bilayer surface, making the phospholipid molecules more accessible to the enzyme active site.

2-Naphthylamine↗

PubMed1995

Reduced alveolar-capillary membrane diffusing capacity in chronic heart failure. Its pathophysiological relevance and relationship to exercise performance.

BACKGROUND: The pulmonary diffusing capacity for carbon monoxide (DLCO) is reduced in chronic heart failure (CHF) and is an independent predictor of peak exercise oxygen uptake. The pathophysiological basis for this remains unknown. The aim of this study was to partition DLCO into its membrane conductance (DM) and capillary blood volume components (Vc) and to assess if alveolar-capillary membrane function correlated with functional status, exercise capacity, and pulmonary vascular resistance. METHODS AND RESULTS: The classic Roughton and Forster method of measuring single-breath DLCO at varying alveolar oxygen concentrations was used to determine DM and Vc in 15 normal subjects and 50 patients with CHF. All performed symptom-limited maximal bicycle exercise tests with respiratory gas analysis; 15 CHF patients underwent right heart catheterization. DLCO was significantly reduced in CHF patients compared with normal subjects, predominantly because of a reduction in DM (7.0 +/- 2.6 versus 12.9 +/- 3.8 versus 20.0 +/- 6.1 mmol.min-1.kPa-1 in New York Heart Association class III, class II, and normal subjects, respectively, P < .0001), even when the reduction in lung volumes was accounted for by the division of DM by the effective alveolar volume. The Vc component of DLCO was not impaired. DM significantly correlated with maximal exercise oxygen uptake (r = .72, P < .0001) and inversely correlated with pulmonary vascular resistance (r = .65, P < .01) in CHF. CONCLUSIONS: Reduced alveolar-capillary membrane diffusing capacity is the major component of impaired pulmonary gas transfer in CHF, correlating with maximal exercise capacity and functional status. DM may be a useful marker for the alveolar-capillary barrier damage induced by raised pulmonary capillary pressure.

Blood-Air Barrier↗

PubMed1995

Staff attitudes toward family involvement in residential treatment centers for children.

OBJECTIVES: The goals of this study were to determine the extent of staff members' support for family involvement in residential treatment centers for children, to examine staff members' beliefs about families and the consequences of their involvement, and to examine the relationship between staff members' support of family involvement and their characteristics, experiences, and beliefs. METHODS: A total of 267 staff members at three residential treatment centers for children with psychiatric disorders or mental retardation or both responded to a survey about their experiences with families, beliefs about families, and support for family involvement. RESULTS: Staff members were very supportive of greater family involvement, although they showed more support for families in the role of service recipients than as decision makers. However, staff members did not believe in family reunification as a goal for the majority of children served. The strongest predictors of staff support for family involvement were positive general beliefs about clients' families, the perception that family involvement was advantageous, and the endorsement of fewer reasons to discourage family involvement. CONCLUSIONS: Residential programs seeking to create a more receptive climate for families should help staff members establish positive attitudes about the families they serve and about families' potential role in successful treatment.

Adult↗

PubMed1994

Quantification of the interaction between lysolecithin and phospholipase A2.

The rate of hydrolysis of phosphatidylcholine bilayers by phospholipase A2 may be either enhanced or inhibited by the presence of lysolecithin depending on the experimental conditions examined. To further understand the relationship of lysolecithin to phospholipase A2 activity, the binding of lysolecithin to phospholipase A2 from the venom of Agkistrodon piscivorus piscivorus was examined by fluorescence spectroscopy. The tryptophan emission intensity of the enzyme was enhanced by 70% upon addition of lysolecithin. The binding isotherm for lysolecithin to the phospholipase A2 estimated from the fluorescence change was biphasic, with a clear break in the curve occurring at the critical micelle concentration of the lysolecithin. Several observations suggested that the phospholipase A2 was capable of hydrolyzing the lysolecithin although at a rate far below that of phospholipid hydrolysis. These experiments were repeated using several other species of phospholipase A2, and the results were found to be general among the enzymes except the lys-49 isozyme from A. p. piscivorus which displayed neither the dependence on the critical micelle concentration for binding nor the ability to hydrolyze lysolecithin. These results were used as the basis for a quantitative analysis of enzyme fluorescence changes that occur during the time course of phospholipid hydrolysis and of the mechanism whereby lysolecithin inhibits the hydrolysis of phosphatidylcholine bilayers by phospholipase A2.

Agkistrodon↗

PubMed1994

The development of a mutation in the precore region of the hepatitis B virus in a chronically infected individual.

Over a 15-year period, a white American woman was observed to have progressive hepatitis B that underwent hepatitis Be antigen (HBeAg) positivity to anti-HBe positivity with development of cirrhosis. This patient was found to have a non-sense mutation in the second codon of the pre-C region of the hepatitis B virus genome after her anti-HBe seroconversion but not in her serum when she was HBeAg+. As controls, serial blood specimens were analyzed from 12 other American patients who spontaneously converted from HBeAg to anti-HBe, who underwent an interferon alfa-associated HBeAg to anti-HBe seroconversion, and who did not seroconvert with interferon alfa therapy. No mutations in the pre-C region were observed to arise in these individuals. In conclusion, non-sense mutations that occur in the pre-C region in locations other than the 28th codon can be associated with HBeAg negative progressive liver disease. This report of a non-sense mutation occurring over time is unusual in that it occurred in a white American patient.

Adult↗

PubMed1994

Family involvement in residential treatment of children with retardation: is there evidence of detachment?

Family involvement could be critical for successful residential treatment. Historically, however, out of home placement for children with mental retardation meant a severing of meaningful ties with their families. Today, families have greater involvement with pre-placement services and might be more involved in residential treatment as well. Families (N = 55) were interviewed twice, approximately one and two years after placement, to assess their involvement with the child and their reactions to placement. Contrary to previous findings, family involvement was high and stable; there was no evidence of behavioral detachment. Moreover, respondents primarily reported post-placement benefits to the family. Family emotional reactions were considered within a framework of "psychological tasks of placement".

Child↗

PubMed1994

Increased alveolar/capillary membrane resistance to gas transfer in patients with chronic heart failure.

OBJECTIVE: To investigate pulmonary diffusive resistance to gas exchange in patients with heart failure and healthy volunteers, assessing the relative contributions of the alveolar/capillary membrane and pulmonary capillary blood. SETTING: Hospital outpatient department and pulmonary function laboratory. PATIENTS: 38 patients (mean age 60) receiving treatment with loop diuretics and angiotensin converting enzyme inhibitors for stable symptomatic heart failure of > 6 months duration (New York Heart Association (NYHA) classes II and III). Results were compared with those of 17 healthy volunteers (mean age 52). METHODS: The alveolar/capillary membrane diffusive resistance and the pulmonary capillary blood volume available for physiological gas exchange were determined by the Roughton and Forster method, which measures the single breath pulmonary diffusing capacity for carbon monoxide at varying alveolar oxygen concentrations. RESULTS: Total pulmonary diffusive resistance was higher in patients than controls. Alveolar/capillary membrane resistance formed the main component of this increase, accounting for a mean (SD) of 63% (20%) and 86% (8%) of total pulmonary diffusive resistance in patients in NYHA II and III classes respectively, compared with 53% (10%) in controls. The pulmonary capillary blood volume was not significantly different between controls and patients in NYHA class II (66 (18) ml v 61 (18) ml), but was increased in those in NYHA class III (95(46) ml, P < 0.05). CONCLUSION: This study confirmed impairment of pulmonary diffusion at rest in patients with chronic heart failure and identified impaired alveolar/capillary membrane function as the main factor responsible.

Adult↗

PubMed1993

Quantification of the interaction of lysolecithin with phosphatidylcholine vesicles using bovine serum albumin: relevance to the activation of phospholipase A2.

The activity of soluble phospholipase A2 to hydrolyze phosphatidylcholine vesicles increases abruptly after a lag time of several minutes. The onset of this apparent activation event probably results from the accumulation of a threshold mole fraction of the hydrolysis products (lysolecithin and fatty acid) in the bilayer. One important observation relevant to the mechanism of this activation process is the biphasic dependence of the lag time on vesicle concentration. To test whether this dependence can be attributed entirely to the strength of partitioning of the lysolecithin into the phosphatidylcholine bilayer, we estimated the apparent partition coefficient of lysophospholipid in the membrane of phosphatidylcholine vesicles. Based on competition between bovine serum albumin and the vesicles for the lysophospholipid, we estimated the partition coefficient to be about 5.10(-7) for palmitoyl lipids at 39 degrees C and about 9.10(-7) for myristoyl lipids at 22 degrees C. These values were able to rationalize the behavior of the lag time with dipalmitoylphosphatidylcholine vesicles, but they were unable to predict the behavior with dimyristoylphosphatidylcholine. Therefore, it appears that the complete dependence of the lag phase on vesicle concentration must be explained by additional means such as the possible contribution of nascent fatty acid or previously proposed kinetic activation mechanisms.

1,2-Dipalmitoylphosphatidylcholine↗