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Biomedical subjects

D Baker

Publications and source records attributed to D Baker.

At least 127 records · Page 7Linked to original sources
PubMed1999

Results of the National Cooperative Inner-City Asthma Study (NCICAS) environmental intervention to reduce cockroach allergen exposure in inner-city homes.

BACKGROUND: Cockroach allergen is important in asthma. Practical methods to reduce exposure are needed. OBJECTIVE: We sought to evaluate the effectiveness of house cleaning and professional extermination on lowering cockroach antigen levels in inner-city dwellings. METHODS: As part of the National Cooperative Inner-City Asthma Study intervention, 265 of 331 families with asthmatic children who had positive skin test responses to cockroach allergen consented to a professional home extermination with 2 applications of a cockroach insecticide (Abamectin, Avert) combined with directed education on cockroach allergen removal. On a random subset of 48 homes undergoing cockroach extermination in the intervention group, Bla g 1 was measured in settled dust from the kitchen, bedroom, and TV/living room. The first sample was collected 1 week before extermination, with additional samples after the exterminations at approximately 2, 6, and 12 months after the first sample. Self-reported problems with cockroaches were collected at baseline and after 12 months of follow-up in both the intervention and control group. RESULTS: The geometric mean kitchen level of Bla g 1 decreased at 2 months (33.6 U/g) relative to preextermination levels (68.7 U/g, P <.05). The percent of kitchens with over 8 U/g of Bla g 1 followed a similar pattern, but only the decrease from preextermination to 6-month levels was significant (86.8% vs 64.3%, P <.05). By the 12-month visit, the allergen burden had returned to or exceeded baseline levels. Except for an increase in the bedroom at 2 months (8.9 U/g vs 11.1 U/g, P <.05), no other significant change was seen. Only about 50% of the families followed the cleaning instructions; no greater effect was found in these homes. Self-reported problems with cockroaches showed no difference between the intervention and control group after 1 year of follow-up. CONCLUSIONS: Despite a significant, but short-lived, decrease the cockroach allergen burden remained well above levels previously found to be clinically significant.

Allergens↗
PubMed1999

Does employment improve the health of lone mothers? The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

In Britain the government is currently proposing legislation that will encourage welfare recipients to gain employment. A central tenet of this 'welfare to work' policy is that employment will not only reduce the poverty of welfare recipients, but also improve their health. This research assessed the extent to which the movement from 'welfare to work' is likely to benefit the mental and physical health of lone mothers with preschool children. The sample was 719 lone mothers and a comparison group of 8779 women with partners drawn from the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC). Data collected by self completion questionnaire at 33 months postpartum provided information about average weekly take home family income and the mother's employment status. The health outcomes measured were general well being, both minor and major depression (using the Edinburgh Postnatal Depression Scale), self report of respiratory symptoms (cough/cold, wheeze, influenza) from 18-33 months postpartum and self report of symptoms common in the childbearing years (backache, haemorrhoids) also from 18-33 months postpartum. Lone mothers who were not employed were the poorest group in the sample; 94% of this group (402) had a family income of less than pound sterling 200 per week, compared with 72% (188) of lone mothers who were employed, 25% (905) of partnered women who were not employed and 12% (466) of partnered women who were employed. Lone mothers were significantly more likely than women with partners to report poorer well being (chi2 = 11.7, df = 3, P = 0.01), to have a major depressive disorder (chi2 = 92.6, df = 1, P = 0.0001) and to report wheeze (chi2 = 31.1, df = 1, P = 0.0001), but significantly less likely to report cough/cold (chi2 = 9.9, df = 1, P = 0.0001) or haemorrhoids (chi2 = 16.6, df = 1, P = 0.0001). Lone mothers who were unemployed and living on less than pound sterling 100 per week were significantly more likely to be depressed (chi2 = 3.9, df = 1, P = 0.05) than those who were employed and living on pound sterling 200 or more per week, and significantly less likely to report cough/cold (chi2 = 3.8, df = 1, P = 0.05). Logistic regression analyses showed no significant independent association between employment and better health for lone mothers. Rather, when compared with lone mothers who were not working, those who were employed were more likely to report minor respiratory symptoms such as cough/cold (OR = 1.51, 95% CI = 1.00,2.31). Overall, the results suggested that the movement from 'welfare to work' is unlikely to improve the health of lone mothers.

Adult↗
PubMed1999

Matching theory and experiment in protein folding.

There has been considerable progress made over the past year in linking experimental and theoretical approaches to protein folding. Recent results from several independent lines of investigation suggest that protein folding mechanisms and landscapes are largely determined by the topology of the native state and are relatively insensitive to details of the interatomic interactions. This dependence on low-resolution structural features, rather than high-resolution detail, suggests that it should be possible to describe the fundamental physics of the folding process using relatively low-resolution models. Recent experiments have set benchmarks for testing new models and progress has been made in developing theoretical models for interpreting and predicting experimental results.

Diffusion↗
PubMed1999

Experiment and theory highlight role of native state topology in SH3 folding.

We use a combination of experiments, computer simulations and simple model calculations to characterize, first, the folding transition state ensemble of the src SH3 domain, and second, the features of the protein that determine its folding mechanism. Kinetic analysis of mutations at 52 of the 57 residues in the src SH3 domain revealed that the transition state ensemble is even more polarized than suspected earlier: no single alanine substitution in the N-terminal 15 residues or the C-terminal 9 residues has more than a two-fold effect on the folding rate, while such substitutions at 15 sites in the central three-stranded beta-sheet cause significant decreases in the folding rate. Molecular dynamics (MD) unfolding simulations and ab initio folding simulations on the src SH3 domain exhibit a hierarchy of folding similar to that observed in the experiments. The similarity in folding mechanism of different SH3 domains and the similar hierarchy of structure formation observed in the experiments and the simulations can be largely accounted for by a simple native state topology-based model of protein folding energy landscapes.

Amino Acid Sequence↗
PubMed1999

Chain collapse can occur concomitantly with the rate-limiting step in protein folding.

We have directly characterized the extent of chain collapse early in the folding of protein L using time-resolved small angle X-ray scattering. We find that, immediately after the initiation of refolding, the protein exhibits dimensions indistinguishable from those observed under highly denaturing, equilibrium conditions and that this expanded initial state collapses with the same rate as that of the overall folding reaction. The observation that chain compaction need not significantly precede the rate-limiting step of folding demonstrates that rapid chain collapse is not an obligatory feature of protein folding reactions.

Bacterial Proteins↗
PubMed1999

Graduated compression stockings in the prevention of venous thromboembolism.

BACKGROUND: Surveys still show a wide variation in routine use of deep vein thrombosis (DVT) prophylaxis despite its established place in current patient management. This article reviews the mechanism of action, efficacy and complications of stockings in preventing DVT. METHODS: Relevant publications indexed in Medline (1966-1998) and the Cochrane database were identified. Appropriate articles identified from the reference lists of the above searches were also selected and reviewed. RESULTS AND CONCLUSION: Graduated compression stockings reduce the overall cross-sectional area of the limb, increase the linear velocity of venous flow, reduce venous wall distension and improve valvular function. Fifteen randomized controlled trials of graduated compression stockings alone were reviewed. Stockings reduced the relative risk of DVT by 64 per cent in general surgical patients and 57 per cent following total hip replacement. The effect of stockings was enhanced by combination with pharmacological agents such as heparin; the combination is recommended in patients at moderate or high risk of DVT. Knee-length stockings are as effective and should replace above-knee stockings. Complications are rare and avoidable.

Bandages↗
PubMed1999

CD44 is involved in selective leucocyte extravasation during inflammatory central nervous system disease.

Clinical signs of experimental autoimmune encephalomyelitis (EAE) are associated with the selective recruitment of CD4+ memory (CD45RBlow CD44high) T cells into the central nervous system (CNS). However, we have found that many of these recently recruited memory cells are CD44low, suggesting that the CD44 antigen may be involved in, and transiently lost during, the extravasation process. Indeed, administration of a CD44-specific antibody (IM7.8.1) induced leucocyte CD44 shedding and both prevented the development and ameliorated the severity of established EAE by inhibiting mononuclear cell infiltration into the CNS. Trafficking of cells into lymph nodes, however, a property mainly of naïve cells, was essentially unaffected. In contrast, treatment with antibody to very late activation antigen-4 (VLA-4) prevented homing to both the CNS and to lymph nodes. This study contests previous reports that dismissed a role for CD44 in inflammation of the CNS and, coupled with observations in murine dermatitis and arthritis, suggests that CD44 is involved in the homing of primed lymphocytes to sites of inflammation. CD44 should therefore be considered a target for immunotherapy of T-cell-mediated inflammatory diseases, such as multiple sclerosis.

Animals↗
PubMed1999

Robustness of protein folding kinetics to surface hydrophobic substitutions.

We use both combinatorial and site-directed mutagenesis to explore the consequences of surface hydrophobic substitutions for the folding of two small single domain proteins, the src SH3 domain, and the IgG binding domain of Peptostreptococcal protein L. We find that in almost every case, destabilizing surface hydrophobic substitutions have much larger effects on the rate of unfolding than on the rate of folding, suggesting that nonnative hydrophobic interactions do not significantly interfere with the rate of core assembly.

Amino Acid Substitution↗
PubMed1999

Differences between infants and adults in the social aetiology of wheeze. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

OBJECTIVES: To compare the relation between relative deprivation, its associated social risk factors and the prevalence of wheeze in infancy and in adulthood. DESIGN: A cross sectional population study. SETTING: The three District Health Authorities of Bristol. SUBJECTS: A random sample of 1954 women stratified by age and housing tenure to be representative of women with children < 1 in Great Britain and selected from the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC). MAIN OUTCOME MEASURES: The prevalence of wheeze for infants at six months after birth and for their mothers and fathers at eight months postpartum. Potential mediators of the relation between relative deprivation and wheeze measured were overcrowded living conditions, number of other siblings in the household, damp or mouldy housing conditions, maternal and paternal smoking behaviour, and infant feeding practice. RESULTS: 63.4% (1239) of the sample lived in owner occupied/mortgaged accommodation (relatively affluent) and 36.6% (715) lived in council house/rented accommodation (relatively deprived). Wheeze was significantly more likely for infants living in council house/rented accommodation (chi 2 = 15.93, df = 1, p < 0.0001), their mothers (chi 2 = 9.28, df = 1, p < 0.001) and their fathers (chi 2 = 7.41, df = 1, p < 0.01). For those living in council house/rented accommodation backward stepwise logistic regression analyses showed that infants with other siblings in the household were significantly more likely to wheeze (OR = 1.83, 95% CI = 1.27, 2.65), as were infants whose mothers smoked (OR = 1.82, 95% CI = 1.30, 2.55) and those who were breast fed for less than three months (OR = 0.66, 95% CI = 0.44, 0.98). Mothers with a partner who smoked were significantly more likely to report wheeze (OR = 1.73, 95% CI = 1.05, 2.85). There was no independent association between the social factors included in the analysis and the likelihood of wheeze for fathers. CONCLUSIONS: This study identified differences in the social factors associated with a higher prevalence of wheeze in infancy and in adulthood; results suggested that this symptom was commonly linked to infection in infancy, but not in adulthood. While environmental tobacco smoke was associated with a higher prevalence of wheeze in infancy and in adulthood, this does not necessarily indicate a common underlying mechanism; possible explanations are discussed.

Cohort Studies↗
PubMed1999

Dot immunobinding assay for detection of bovine herpesvirus 4 antibodies in rabbits.

A dot immunobinding assay (DIA) was used for the detection of antibody against bovine herpesvirus 4 (BHV-4) in experimentally infected specific-pathogen-free male and female rabbits. A semipurified virus preparation was used as the antigen, and protein A/G-horseradish-peroxidase conjugate and diaminobenzidine tetrahydrochloride were used as the detection system. Results of the DIA procedure on serum samples of experimentally infected male and female rabbits were compared with those of a complement-dependent virus neutralization (VN) test. None of the tested sera (0/60 samples) from either male or female rabbits were positive by the complement-dependent VN test. Results of the DIA procedure for the same tested sera were positive in 35 of 60 samples (58%) from BHV-4 infected rabbits, indicating higher sensitivity of DIA procedure as compared with the complement-dependent VN test.

Animals↗
PubMed1999

Satiation, capacity, and within-session responding.

Responding may change substantially over the course of a session (McSweeney, Hinson, & Cannon, 1996). The role of satiation in this effect was investigated in three experiments. Experiment 1 showed that the capacity of pigeons to consume milo over a 1-hr period was relatively stable across three different methods of measurement. In Experiment 2, pigeons were divided into two groups that differed in their capacity based on one of those measures. Key pecking was then reinforced under a variable-interval 30-s schedule with hopper durations of 2 or 5 s. According to the satiation hypothesis, subjects with small capacities should satiate faster and therefore show greater decreases in food-reinforced responding than would subjects with larger capacities. The results confirmed this prediction and showed that the magnitudes of within-session decreases were better predicted by the amount an animal consumed relative to its capacity than by absolute amount alone. In Experiment 3, each pigeon was prefed 0, 5, 15, or 25 g of milo prior to each session. Consistent with the satiation hypothesis, increases in prefeeding produced lower overall response rates in the smaller capacity subjects than in the larger capacity subjects at each level of prefeeding. These experiments demonstrate the importance of a new variable in the control of behavior, and provide a recommended technique for its measurement.

Animals↗
PubMed1999

Good manufacturing practice (GMP) compliance in the biologics sector: plasma fractionation.

The U.S. blood supply is the safest it has ever been. Due to blood safety and the introduction of viral inactivation/clearance technologies, protein therapies derived from human blood have also in recent years had a history of product safety. Nevertheless, since 1995, the plasma-fractionation industry has experienced increased compliance-related actions by the Food and Drug Administration (FDA), as shown by a substantive increase in the number of FDA 483 inspectional observations, FDA warning letters and other FDA regulatory action. An evaluation of these trends shows that they reflect the implementation by the FDA of increased inspectional interest in the plasma-fractionation industry and an evolution of inspectional practices and standards of current good manufacturing practice (cGMP). Plasma fractionators have responded to FDA actions by carefully evaluating and addressing each inspectional observation, assessing impact to product and taking appropriate actions, including corrective actions to prevent future occurrence. They have made major investments in facilities, quality systems, personnel and training to meet the evolving standards of cGMP and in an effort to implement these standards systemically. Through industry associations, manufacturers have further enhanced product safety by adopting additional voluntary standards for plasma to prevent the entry of potentially unsuitable plasma into the production process. The industry remains committed to application of cGMP and to working with the FDA in further evolution of these standards while striving to assure a continued supply of safe, pure and effective plasma-derived therapies.

Biotechnology↗
PubMed1998

The single helix in protein L is largely disrupted at the rate-limiting step in folding.

To investigate the role of helix formation in the folding of protein L, a 62 residue alpha/beta protein, we studied the consequences of both single and multiple mutations in the helix on the kinetics of folding. A triple mutant with 11 additional carbon atoms in core residues in the amino-terminal portion of the helix folded substantially faster than wild type, suggesting that hydrophobic association with residues elsewhere in the protein occurs at the rate-limiting step in folding. However, helix-destabilizing mutations had little effect on the rate of folding; in particular, a triple glycine substitution on the solvent-exposed side of the helix increased the unfolding rate 56-fold while reducing the folding rate less than threefold. Thus, in contrast to the predictions of models of folding involving the coalescence of well-formed secondary structure elements, the single helix in protein L appears to be largely disrupted at the rate-limiting step in folding and unfolding.

Bacterial Proteins↗
PubMed1998

Limited internal friction in the rate-limiting step of a two-state protein folding reaction.

Small, single-domain proteins typically fold via a compact transition-state ensemble in a process well fitted by a simple, two-state model. To characterize the rate-limiting conformational changes that underlie two-state folding, we have investigated experimentally the effects of changing solvent viscosity on the refolding of the IgG binding domain of protein L. In conjunction with numerical simulations, our results indicate that the rate-limiting conformational changes of the folding of this domain are strongly coupled to solvent viscosity and lack any significant "internal friction" arising from intrachain collisions. When compared with the previously determined solvent viscosity dependencies of other, more restricted conformational changes, our results suggest that the rate-limiting folding transition involves conformational fluctuations that displace considerable amounts of solvent. Reconciling evidence that the folding transition state ensemble is comprised of highly collapsed species with these and similar, previously reported results should provide a significant constraint for theoretical models of the folding process.

Bacterial Proteins↗