PubMed Health⌕ Search

Biomedical subjects

T E Weaver

Publications and source records attributed to T E Weaver.

At least 73 records · Page 4Linked to original sources
PubMed1986

In vitro acetylation of rat pulmonary surfactant-associated glycoprotein(s) A primary translation products.

The primary translation products of pulmonary surfactant-associated glycoprotein(s) A, the major apolipoprotein in mammalian surfactants, exhibit extensive charge heterogeneity. After in vitro translation of poly(A)+ mRNA from rat lung, the primary translation products of glycoprotein(s) A were identified as a charge train of five proteins of 26 kDa (pI 4.6-5.0), the predominant forms being the more acidic members (pI less than 4.8). Inhibition of acetylation during in vitro translation of rat lung poly(A)+ mRNA resulted in a predominance of the more basic isoforms (pI greater than or equal to 4.8). Intracellular forms of glycoprotein(s) A were immunoprecipitated from rat Type II epithelial cells after treatment with tunicamycin or after deglycosylation with endoglycosidase H. Five intracellular precursors consisting primarily of acidic members of the charge train were identified, this being consistent with the intracellular acetylation of the protein. In contrast, canine glycoprotein(s) A translation products consisted of only three proteins of 26 kDa (pI 4.8-5.0), in which most of the radiolabel was concentrated in the more basic components. Acetylation may account for some, but not all, of the charge heterogeneity in the primary translation products and processed forms of surfactant-associated glycoprotein(s) A in the rat.

Acetylation↗
PubMed1986

Synthesis of surfactant-associated protein, 35,000 daltons, in fetal lung.

The major human pulmonary surfactant-associated protein of 35,000 daltons (Da) (SAP-35), consists of a group of related proteins of 27,000-36,000 Da, with isoelectric points ranging from pH 4.6 to 5.2. SAP-35 precursors were identified by immunoprecipitation of protein products of in vitro translation of normal adult human poly(A)+ mRNA with human SAP-35 antiserum. The translation products nearly comigrated with the most basic components of alveolar SAP-35 (mol mass = 24,500-27,000 Da). Processing of the primary translation products by canine pancreatic microsomal membranes increased their apparent molecular weight to 29,000-30,000-Da forms, which were sensitive to endoglycosidase F, suggesting the addition of asparagine-linked oligosaccharides to the molecules. A smaller protein of 24,500 Da was generated during treatment with canine microsomal membranes likely representing cleavage of a signal peptide. SAP-35 was not detected in explants of [35S]methionine-labeled fetal lung (20-24 wk gestation) after 1 day of culture or immunoprecipitates of in vitro translated poly(A)+ mRNA isolated from fetal human lung. However, after 3-5 days of organ culture, synthesis of SAP-35 was readily detected by immunoprecipitation of [35S] methionine-labeled tissue. Fully sialylated (neuraminidase-sensitive forms) comigrated with fully glycosylated SAP-35 isolated from human surfactant. High mannose (endoglycosidase H-sensitive precursors) were also synthesized by the organ cultures and were distinct from the secreted form in surfactant. Synthesis of surfactant-associated SAP-35 and its precursors was induced in association with morphological maturation of the type II epithelial cell during organ culture of human fetal lung.

Chemical Phenomena↗
PubMed1986

Immunologic identification of a pulmonary surfactant-associated protein of molecular weight = 6000 daltons.

Hydrophobic, small molecular weight, surfactant-associated protein of Mr = 6000 (SAP-6) was isolated from bovine, canine, and human alveolar lavage and identified by silver staining after sodium dodecyl sulfate polyacrylamide gel electrophoresis gels. Lesser amounts of protein of Mr = 14,000, 20,000, and 26,000 daltons also copurified with SAP-6, likely representing oligomers of the Mr = 6,000 dalton protein. In the absence of sulfhydryl-reducing agents, increased amounts of the larger forms of the protein were observed. Antisera generated against bovine SAP-6 were used to further characterize the protein and distinguish it from the more abundant surfactant-associated glycoprotein of Mr = 35,000 (SAP-35) present in mammalian surfactants. Rabbit antisera generated against the bovine hydrophobic protein recognized SAP-6 and lesser amounts of the proteins of Mr = 14,000, 20,000, and 26, 000 daltons. The SAP-6 antisera were reactive against the hydrophobic proteins from human, bovine, and canine surfactants as assessed by immunoblot analysis after sodium dodecyl sulfate polyacrylamide gel electrophoresis. SAP-6 antisera did not detect bovine SAP-35 the abundant surfactant-associated glycoprotein, by immunoblot analysis; however, some reactivity of the anti-SAP-6 was detected against purified bovine SAP-35 by a sensitive enzyme-linked immune-adsorbant assay. Anti-SAP-6-did not react with bovine serum components either by immunoblot or by enzyme-linked immune-adsorbant assay. Monospecific antisera generated against bovine SAP-35 did not detect SAP-6 by immunoblot analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Intracellular and oligomeric forms of surfactant-associated apolipoproteins(s) A in the rat.

Sulfhydryl-dependent oligomeric forms of the surfactant-associated apolipoprotein(s) A, obtained from particulate preparations of adult rat lung lavage, were characterized by immunoblot analysis and by silver staining of proteins separated by one- and two-dimensional SDS-polyacrylamide gel electrophoresis. Under non-reducing conditions, these proteins migrated as oligomers, Mr approx. 50-70, 115, 160 kDa and greater. The large oligomers were reduced to the apolipoprotein(s) A subunits by treatment with beta-mercaptoethanol; Mr 38 (A3), 32 (A2) and 26 kDa (A1), pI 4.2-4.8. Mr 50 kDa protein was composed of sulfhydryl-dependent homo-dimers of protein(s) A1 (Mr 26 kDa). 55 kDa protein was a hetero-dimer composed primarily of A1 and A2 (Mr 26 and 32 kDa). 62 kDa protein was composed of hetero-dimers of A3 and apolipoprotein A2 (Mr 38 and 32 kDa). 70 kDa protein was a homodimer composed of apolipoprotein A3 A3 (38 kDa). Larger molecular forms were composed primarily of 38 and 32 kDa and lesser amounts of 26 kDa. Treatment with endoglycosidase F reduced A2 and A3 to 26 kDa. Apolipoprotein A1 co-migrated with a protein of Mr 26 kDa immunoprecipitated from [35S]methionine-labelled Type II epithelial cells. Chymotryptic-tryptic peptide maps of apolipoproteins A1, A2 and A3 were identical, suggesting that apolipoproteins A3 and A2 arise through extensive glycosylation of apolipoprotein A1.

Animals↗
PubMed1985

Identification of canine pulmonary surfactant-associated glycoprotein A precursors.

Surfactant-associated glycoproteins A were identified by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis of crude surfactant from canine alveolar lavage: an unglycosylated form (protein A1), 27,000-28,000 daltons; glycoprotein A2, 32,000-34,000 daltons; and glycoprotein A3, 37,000-38,000 daltons; pH at isoelectric point (pI) 4.5-5.0. Glycoproteins A2 and A3 were electroeluted and used to prepare a monospecific antiserum that identified proteins A1, A2, and A3 in immunoblots of crude surfactant obtained from dog lung lavage. This antiserum precipitated several proteins from in vitro translated canine lung poly(A)+ mRNA; proteins of 27,000 daltons, pI 5.0, and 28,000 daltons, pI 4.8-5.0, which precisely comigrated with proteins A1 from canine surfactant. Cotranslational processing of the primary translation products by canine pancreatic microsomal membranes resulted in larger proteins of 31,000-34,000 daltons, pI 4.8-5.0. Treatment of these processed forms of glycoprotein A with endoglycosidase F, to remove N-linked carbohydrate, resulted in proteins of 27,000-28,000 daltons which precisely comigrated with surfactant protein A1. These observations demonstrate that the polypeptide precursors to the glycoproteins A complex are extensively modified by addition of asparagine N-linked complex carbohydrate and are subsequently secreted as glycoproteins A2 and A3.

Animals↗
PubMed1984

Acetazolamide teratogenesis: association of maternal respiratory acidosis and ectrodactyly in C57BL/6J mice.

Exposure of C57BL/6J mice to CO2 during a critical period of gestation results in predominantly right-sided, postaxial, forelimb ectrodactyly in the offspring. The incidence and severity of CO2-induced limb malformations has been shown to be dependent on the concentration of inspired CO2, the developmental age of the embryo at exposure and the duration of CO2 exposure. Offspring of acetazolamide-treated C57BL/6J mice also display this highly specific form of ectrodactyly (Green et al., '73). Since the drug has been shown to elevate tissue CO2 tension (Mithoefer and Davis, '58), the teratogenic effect of acetazolamide may be related to induction of a hypercapnic embryonic environment.

Abnormalities, Drug-Induced↗
PubMed1984

Acetazolamide teratogenesis: interaction of maternal metabolic and respiratory acidosis in the induction of ectrodactyly in C57BL/6J mice.

Exposure of C57BL/6J mice to 20% CO2 for 8 hours on day 10 of gestation has been shown to produce right-sided postaxial forelimb ectrodactyly in 23% of the offspring. Carbon dioxide exposure produces a dramatic increase in maternal plasma CO2 accompanied by an inevitable decrease in plasma pH, both of which appear to be involved in the induction of ectrodactyly. However, the low incidence of ectrodactyly associated with NH4Cl-induced metabolic acidosis suggests that the primary teratogenic factor in respiratory acidosis is elevated CO2 tension. This conclusion is supported by the observation that moderation of maternal plasma pH in the face of sustained elevated PCO2 fails to reduce the incidence of ectrodactyly; moreover, there is a strong correlation between maternal serum CO2 content and the incidence of ectrodactyly.

Abnormalities, Drug-Induced↗
PubMed1984

Comparative inhalation teratogenicity of four glycol ether solvents and an amino derivative in rats.

Previous research demonstrated the inhalation teratogenicity of the solvent 2-ethoxyethanol in rats and rabbits. As this is one of a class of widely used industrial solvents, we investigated the teratogenicity of five structurally related compounds. Each chemical was vaporized and administered to approximately 15 pregnant rats in one to three concentrations for 7 hr/day on gestation days 7 to 15, and dams were sacrificed on day 20. Fetuses were individually weighed, and two-thirds of them were fixed in Bouin's solution and examined for soft-tissue anomalies. The other one-third were fixed in alcohol, stained with Alizarin Red and examined for skeletal defects. Data were analyzed on a litter basis; three solvents were compared with a pooled group (N = 34) of sham-exposed controls, and the remaining two were compared with a group of 15 controls. At concentrations which were apparently not maternally toxic, 2-methoxyethanol was highly embryotoxic, producing complete resorptions at 200 ppm; increased resorptions, reduced fetal weights and skeletal and cardiovascular defects occurred at both 100 and 50 ppm. 2-ethoxyethyl acetate at 600 ppm induced complete resorption of litters; 390 ppm reduced fetal weights and induced skeletal and cardiovascular defects, but only a single defect was observed at 130 ppm. 2-Butoxyethanol evidenced slight maternal toxicity at 200 ppm but produced no increase in congenital defects at that concentration. Neither 2-(2-ethoxyethoxy)ethanol (100 ppm) nor 2-methylaminoethanol (150 ppm) was maternally toxic or embryotoxic. In summary, shorter alkyl chained glycol ethers produced greater embryotoxicity than those having longer chains, and the ester produced effects equivalent to the ether, both patterns predictable from the biochemical literature.

Abnormalities, Drug-Induced↗
PubMed1981

Vascular hypervolemia and hematoma formation in chick embryos treated with trypan blue.

The relationship between cardiovascular disturbances and the formation of hematomas in trypan blue-treated chick embryos was investigated. Hematocrits from Hamburger-Hamilton stage 15 and 16 embryos (8-10 hours after treatment at stage 13) were obtained. The hematocrit value from the treated embryos was significantly lower (P less than 0.001) than the values from controls. Unopened and saline-injected control values were not significantly different (P greater than 0.05). We interpret this to mean that there is excess circulating fluid volume in the treated embryos. The results of direct injection of measured volumes of fluid into the cardiovascular system of normally developing embryos (stages 15 and 16) provided evidence to suggest that the caudal dorsal aortae are susceptible to fluid-induced distension and rupture.

Animals↗
PubMedDate not supplied

An explanatory model of functional status in chronic obstructive pulmonary disease.

The purpose of this study was to test an explanatory model of variables influencing functional status in chronic obstructive pulmonary disease (COPD). The sample consisted of 104 patients with COPD (85 males, 19 females, mean age = 65.5, SD = 7.7). The variables in the initial model were age, length of illness, pulmonary function, oxygen desaturation during exercise, dyspnea, depressed mood, anxiety, self-esteem, exercise capacity, and functional status. Path analysis revealed that exercise capacity (beta = .337, p = .0007), dyspnea (beta = .324, p = .0009), and depressed mood (beta = -.204, p = .011) directly influenced functional status Dyspnea (beta = .488, p < .0001), depression (beta = -.217, p = .003), and pulmonary function (beta = .421, p < .0001) indirectly influenced functional status through exercise capacity. Self-esteem (beta = -.492, p = .004) and anxiety (beta = .696, p < .0001) indirectly influenced functional status through depressed mood. The findings of this study suggest that efforts to improve functional status of individuals with COPD should focus on interventions that influence exercise capacity, dyspnea, anxiety, and depressed mood.

Activities of Daily Living↗