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F Baldwin

Publications and source records attributed to F Baldwin.

At least 19 recordsLinked to original sources
PubMed2001

Lipid binding-induced conformational change in human apolipoprotein E. Evidence for two lipid-bound states on spherical particles.

Apolipoprotein (apo) E contains two structural domains, a 22-kDa (amino acids 1-191) N-terminal domain and a 10-kDa (amino acids 223-299) C-terminal domain. To better understand apoE-lipid interactions on lipoprotein surfaces, we determined the thermodynamic parameters for binding of apoE4 and its 22- and 10-kDa fragments to triolein-egg phosphatidylcholine emulsions using a centrifugation assay and titration calorimetry. In both large (120 nm) and small (35 nm) emulsion particles, the binding affinities decreased in the order 10-kDa fragment approximately 34-kDa intact apoE4 > 22-kDa fragment, whereas the maximal binding capacity of intact apoE4 was much larger than those of the 22- and 10-kDa fragments. These results suggest that at maximal binding, the binding behavior of intact apoE4 is different from that of each fragment and that the N-terminal domain of intact apoE4 does not contact lipid. Isothermal titration calorimetry measurements showed that apoE binding to emulsions was an exothermic process. Binding to large particles is enthalpically driven, and binding to small particles is entropically driven. At a low surface concentration of protein, the binding enthalpy of intact apoE4 (-69 kcal/mol) was approximately equal to the sum of the enthalpies for the 22- and 10-kDa fragments, indicating that both the 22- and 10-kDa fragments interact with lipids. In a saturated condition, however, the binding enthalpy of intact apoE4 (-39 kcal/mol) was less exothermic and rather similar to that of each fragment, supporting the hypothesis that only the C-terminal domain of intact apoE4 binds to lipid. We conclude that the N-terminal four-helix bundle can adopt either open or closed conformations, depending upon the surface concentration of emulsion-bound apoE.

Apolipoproteins E↗
PubMed2000

Effects of lipid interaction on the lysine microenvironments in apolipoprotein E.

Lysines in apolipoprotein (apo) E are key factors in the binding of apoE to the low density lipoprotein receptor, and high affinity binding requires that apoE be associated with lipid. To gain insight into this effect, we examined the microenvironments of the eight lysines in the 22-kDa fragment of apoE3 (residues 1-191) in the lipid-free and lipid-associated states. As shown by (1)H,(13)C heteronuclear single quantum coherence nuclear magnetic resonance, lysine resonances in the lipid-free fragment were poorly resolved over a wide pH range, whereas in apoE3.dimyristoyl phosphatidylcholine (DMPC) discs, the lysine microenvironments and protein conformation were significantly altered. Sequence-specific assignments of the lysine resonances in the spectrum of the lipidated 22-kDa fragment were made. In the lipid-free protein, six lysines could be resolved, and all had pK(a) values above 10. In apoE3.DMPC complexes, however, all eight lysines were resolved, and the pK(a) values were 9.2-11.1. Lys-143 and Lys-146, both in the receptor binding region in helix 4, had unusually low pK(a) values of 9.5 and 9.2, respectively, likely as a result of local increases in positive electrostatic potential with lipid association. Shift reagent experiments with potassium ferricyanide showed that Lys-143 and Lys-146 were much more accessible to the ferricyanide anion in the apoE3.DMPC complex than in the lipid-free state. The angle of the nonpolar face of helix 4 is smaller than the angles of helices 1, 2, and 3, suggesting that helix 4 cannot penetrate as deeply into the DMPC acyl chains at the edge of the complex and that its polar face protrudes from the edge of the disc. This increased exposure and the greater positive electrostatic potential created by interaction with DMPC may explain why lipid association is required for high affinity binding of apoE to the low density lipoprotein receptor.

Apolipoproteins E↗
PubMed2000

Amish country doctor.

Explore the source record for details and available documents.

Amino Acid Metabolism, Inborn Errors↗
PubMed1999

Evaluation of pressure changes in a new design tracheal tube cuff, the Portex Soft Seal, during nitrous oxide anaesthesia.

We have measured pressure changes in a newly designed tracheal tube cuff, the Portex Soft Seal, during nitrous oxide anaesthesia compared with a Mallinckrodt Lo-Contour tube and a Portex Profile tube. The pressure increases in both control groups were significantly greater than those with the new design (P < 0.0001 in each case). The mean increase in pressure in the Mallinckrodt Lo-Contour tube cuff was 9.9 (SD 3.4) mm Hg compared with 10.3 (1.8) mm Hg in the Portex Profile tube cuff and 2.1 (1.5) mm Hg in the Portex Soft Seal tube cuff. We conclude that the Portex Soft Seal cuff prevented a significant increase in intracuff pressure during nitrous oxide anaesthesia.

Adolescent↗
PubMed1994

Basal cells in human bronchial epithelium.

The morphology and distribution of basal cells were investigated in adult human bronchial epithelium. In both smokers and non-smokers typical basal cells were more numerous than atypical basal cells, which were distinguished by their spindle-shaped nucleus, polar cytoplasm, and processes that extended along the basal lamina. The nucleus of the atypical basal cell was consistently closer to the muco-ciliary surface than was the nucleus of the typical basal cell. In cross-sections of bronchi the numbers of typical basal cells/mm epithelium were greatest in large airways; in smaller bronchi (i.e., generations 7-16) the frequency declined. The numbers of atypical basal cells/mm epithelium were similar throughout the bronchial tree. Throughout the bronchial tree both types of basal cells contributed to the maintenance of epithelial cohesion by providing desmosomal attachment for columnar cells. The importance of typical basal cells in this role was indicated by their greater numbers, which collectively presented a large surface for epithelial cell attachment by desmosomes. The surface presented by the cell body and processes of each atypical basal cell for attachment of columnar cells by desmosomes was extensive. If the basal cell is the most important progenitor of bronchial epithelium and the cell at risk in the development of lung cancer, the presence of more basal cells in upper airways, where many lung cancers originate, may be significant. The basal cell populations in larger bronchi are perhaps the greatest concentration of cells with proliferative capability and potential for neoplastic transformation in the human bronchial tree.

Bronchi↗
PubMed1994

Pulmonary hypertension and vascular remodeling in fetal sheep.

Vascular remodeling is commonly associated with pulmonary hypertension (PH) postnatally, but little is known about its presence in fetuses. In sixteen fetal sheep (126 wk gestation), the ductus arteriosus (DA) was ligated, and the animals were studied at 4, 8, and 14 days after surgery. The uninstrumented twins served as controls. Four days post-DA ligation PH resulted in an increase in the right and left ventricular free wall weight ratio (1.2 +/- 0.1 vs. 1.0 +/- 0.1 in the controls; P < 0.01), with a further progressive increase at 8 (1.4 +/- 0.1 vs. 1.0 +/- 0.1; P < 0.01) and 14 days (1.5 +/- 0.2 vs. 1.0 +/- 0.1; P < 0.01). An increase in vascular percent medial thickness was observed after 4 days of DA ligation and was restricted to small vessels. The large arteries collagen and elastin contents were 28.9 +/- 3.4 and 27.1 +/- 3.4 micrograms/micrograms of DNA, respectively, and were not significantly different from control values even after 14 days DA ligation. We further compared elastin synthesis in fetal and neonatal arteries in vitro. Synthesis in the fetus was greater than the newborn (10.6 +/- 1.4 vs. 4.6 +/- 0.7 cpm.mg wet wt-1.h-1; P < 0.01). Vessel endothelium denudation reduced synthesis to 60 +/- 8% of controls in the fetus, whereas no change was seen in the newborn. After an increase in wall stress, synthesis increased in the fetus (194 +/- 28% of control P < 0.01) and newborn (173 +/- 25%; P < 0.01). Removal of the endothelium abolished the response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Linking up with MEDLINE.

Pennsylvania physicians are joining the technology bandwagon, accessing medical databases from homes and offices equipped with personal computers and telephones. This article provides a brief introduction to these electronic libraries, focusing on one called MEDLINE. A subsequent article will describe how to gain online (telephonic) access to these databases.

Databases, Factual↗
PubMed1994

Medical assistance plans will soon blanket state.

Pennsylvania officials and physicians are piloting three alternative programs to the current Medicaid system in an effort to improve access to care and control rising costs. This article explores and compares the programs and their benefits.

Cost Control↗
PubMed1993

Bronchoalveolar eosinophilic cells in a canine model of asthma: two distinctive populations.

In a canine model of asthma, the identity and relationships of two types of cells with eosinophilic granules found in bronchoalveolar lavage (BAL) were investigated. Five female and three male newborn mongrel dogs were sensitized by intraperitoneal injection of 500 micrograms ragweed in 30 mg aluminum hydroxide repeated weekly for 8 weeks and then biweekly until 16 weeks of age. Three female and two male littermate controls received 30 mg aluminum hydroxide. From 4 months of age, dogs received six breaths of wet-nebulized ragweed solution through an endotracheal tube bimonthly. Bronchoalveolar lavage was performed 2 months or more after the last exposure to ragweed and was repeated 5 hours after ragweed inhalation. Dogs studied were 15 to 38 months of age. Eosinophilic cell populations were determined in BAL and peripheral blood; cells were examined by light and electron microscopy. Two eosinophilic cell types were in BAL: an eosinophil and an atypical cell with globule leukocyte characteristics. Specific microgranules, a constant feature of eosinophils, were prominent in the atypical cell and suggest a relationship to the eosinophil granulocyte series for the atypical cell and cells identified by others as globule leukocytes. In ragweed sensitized animals, there were more eosinophilic cells in BAL fluid and more eosinophils in peripheral blood. There was a proportional increase in BAL eosinophils 5 hours after ragweed inhalation and a corresponding decline in peripheral blood eosinophils. There was no increase in numbers of eosinophils in the sensitized animals; eosinophil and atypical cell numbers in littermate controls were unchanged.

Allergens↗
PubMed1991

Surface to nuclear distances in human bronchial epithelium: relationships to penetration by Rn daughters.

Lung cancer in U miners is thought to be related to the inhalation of particulate Rn daughters. Since the depth of penetration by alpha particles is short, the thickness of the epithelium lining the bronchial tree may be a critical factor in the development of cancers at specific sites in the lung. The objectives of the study were to measure the thickness of the epithelium at all levels of the human bronchial tree, to determine the distances of epithelial nuclei from the mucociliary surface, and to compare these parameters in smokers and nonsmokers. Twenty-nine surgically removed specimens were examined; 26 were from smokers. No significant differences were found between smokers and nonsmokers, allowing us to treat the 29 cases as a homogeneous group. With progressive divisions of the bronchi, the epithelium decreases in thickness, and distances of nuclei from the surface are also less in the peripheral bronchi. Allowing for artefacts of tissue preparation, the mean distance from the mucociliary surface to the underlying nuclei varies between 17 and 38 microns.

Aged↗
PubMed1982

Susceptibility of bovine macrophages to infectious bovine rhinotracheitis virus infection.

Infectious bovine rhinotracheitis virus replicated in cultured bovine alveolar macrophages (AM). However, yields of infectious virus were low, with maximum titers approximately 100 times that of the residual inoculum. Immunofluorescence and electron microscopic studies indicated that the majority of macrophages produced viral antigen, but after infection at a multiplicity of 0.1, only 4.1% of AM produced infectious centers. Virus-infected AM culture supernatants possessed interfering activity, probably due to interferon. Incubation of fresh AM with these fluids rendered them refractory to infection. Although AM from infectious bovine rhinotracheitis virus-immune and -susceptible donors were equally permissive and their susceptibility was unaltered by incubation with bacterial lipopolysaccharide, bovine mammary macrophages which were elicited with lipopolysaccharide became nonpermissive when further incubated for 48 h with 1 microgram of lipopolysaccharide per ml. Under these conditions, infected mammary macrophages failed to synthesize viral DNA, and there was reduced synthesis of "late" viral polypeptides.

Animals↗
PubMed1982

Effect of infectious bovine rhinotracheitis virus infection of calves on cell populations recovered by lung lavage.

Calves were challenge exposed with infectious bovine rhinotracheitis (IBR) virus, and experiments were carried out to determine the presence of virus in the lungs, virus or viral antigen in alveolar macrophages, and alterations in immune functions of alveolar macrophages. In experiment 1, calves were challenge exposed intranasally with IBR virus. Although clinical signs of IBR occurred in all challenge-exposed calves, there was minimal evidence of virus or viral antigen in cells lavaged from their lungs, and macrophage Fc- and complement-receptor activities, phagocytic activity, and ability to mediate antibody-dependent cell cytotoxicity were unaltered. In experiment 2, calves were challenge exposed intranasally or by aerosol with IBR virus strains Colorado-1 and 108, and samples were collected 4 and 6 days after challenge exposure. Virus was isolated from the lungs, and pathologic lesions of greater severity occurred in those calves challenge exposed by aerosol. Less than 0.1% of lavaged cells from challenge-exposed calves produced infectious centers on susceptible cell monolayers. In 1 sample of lavaged cells, approximately 5% of the cells, mainly macrophages, had viral antigen in the cytoplasm, as detected by immunofluorescence. Because of the small proportion of macrophages that appeared to become infected after challenge exposure of calves with IBR virus, it is believed that the effect of IBR virus in predisposing calves to pneumonic pasteurellosis is an indirect, rather than a direct, manifestation of viral infection of macrophages.

Animals↗