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Biomedical subjects

L K Williams

Publications and source records attributed to L K Williams.

17 recordsLinked to original sources

Mechanical stretch promotes alveolar epithelial type II cell differentiation.

Functional maturation of pulmonary alveolar epithelial cells is crucial for extrauterine survival. Mechanical distension and mesenchymal-epithelial interactions play important roles in this process. We hypothesized that mechanical stretch simulating fetal breathing movements is an important regulator of pulmonary epithelial cell differentiation. Using a Flexercell Strain Unit, we analyzed effects of stretch on primary cultures of type II cells and cocultures of epithelial and mesenchymal cells isolated from fetal rat lungs during late development. Cyclic stretch of isolated type II cells increased surfactant protein (SP) C mRNA expression by 150 +/- 30% over controls (P < 0.02) on gestational day 18 and by 130 +/- 30% on day 19 (P < 0.03). Stretch of cocultures with fibroblasts increased SP-C expression on days 18 and 19 by 170 +/- 40 and 270 +/- 40%, respectively, compared with unstretched cocultures. On day 19, stretch of isolated type II cells increased SP-B mRNA expression by 50% (P < 0.003). Unlike SP-C, addition of fibroblasts did not produce significant additional effects on SP-B mRNA levels. Under these conditions, we observed only modest increases in cellular immunoreactive SP-B, but secreted saturated phosphatidylcholine rose by 40% (P < 0.002). These results indicate that cyclic stretch promotes developmentally timed differentiation of fetal type II cells, as a direct effect on epithelial cell function and via mesenchymal-epithelial interactions. Expression of the SP-C gene appears to be highly responsive to mechanical stimulation.

Animals↗

Lice, nits, and school policy.

BACKGROUND: The epidemiology of head lice infestation is poorly understood. Many schools treat all children with nits as though they are contagious. Children with nits but no lice are often removed from school until they are treated and all visible nits are removed. OBJECTIVE: To investigate the probability that children with nits alone will become infested with lice. DESIGNS: Prospective cohort study. SETTING: Two metropolitan Atlanta elementary schools. PARTICIPANTS: A total of 1729 children were screened for head lice. Twenty-eight children (1.6%) had lice, whereas 63 (3.6%) had nits without lice. Fifty of the 63 children (79%) with nits alone completed follow-up. OUTCOME MEASURE: Conversion (ie, becoming infested with lice) within 14 days after initial screening. RESULTS: Nine of 50 children (18.0%) followed for nits alone converted. Although children who converted did not have significantly more nits than did nonconverters, having nits near the scalp was a risk factor for conversion. Seven of 22 children (31.8%) with >/=5 nits within one fourth inch of the scalp converted, compared with 2 of 28 children (7.1%) with fewer (relative risk: 4.45; 95% confidence interval: 1.03-19.35). This risk remained statistically significant after separately stratifying for sex, recent treatment, and total number of nits. CONCLUSIONS: Although having >/=5 nits within one fourth inch of the scalp was a risk factor for conversion, most children with nits alone did not become infested. Policies requiring exclusion from school and treatment for all children with nits alone are likely excessive. Instead, these children may benefit from repeated examination to exclude the presence of crawling lice.lice, pediculus, lice infestations, pediatrics, school.

Animals↗

The effects of 1-nitropyrene, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 7,12-dimethylbenz[a]anthracene on 8-hydroxy-2'-deoxyguanosine levels in the rat mammary gland and modulation by dietary 1,4-phenylenebis(methylene) selenocyanate.

Humans are exposed to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 1-nitropyrene (1-NP) via several environmental sources and both are known mammary carcinogens in rodents, with the former being more potent (K. El-Bayoumy, Y.-H. Chae, P. Upadhyaya, A. Rivenson, K. Kurtzke, B. Reddy, S.S. Hecht, Comparative tumorigenicity of benzo[a]pyrene, 1-nitropyrene, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine administered by gavage to female CD rats, Carcinogenesis 16 (1995) 431-434). Following their metabolic activation, both carcinogens are known to bind covalently to DNA. However, it remains to be determined whether these carcinogens can also induce DNA-base oxidation. Our goal was to determine the effects of PhIP and 1-NP on the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG; a marker of oxidative DNA damage) in rat mammary glands and to evaluate the effect of the chemopreventive agent 1,4-phenylenebis(-methylene)selenocyanate (p-XSC) as an inhibitor of such damage. As an established potent mammary carcinogen, the synthetic 7,12-dimethylbenz[a]anthracene (DMBA) was included in this study. Female CD rats were fed a high-fat AIN-76A diet (23.5% corn oil) supplemented with p-XSC (10 ppm as selenium) or unsupplemented control diet for 1 week. At 50 days of age, each rat (12 rats/group) was gavaged with either PhIP (22 mg (100 micromol) per rat) or I-NP (20 mg (80 micromol) per rat) in trioctanoin (0.5 ml), DMBA (5 mg (20 micromol) per rat] in olive oil (0.2 ml), or the corresponding vehicle. Rats were sacrificed 6 and 24 h after carcinogen treatment (six rats per time point). Mammary fat pads were excised and DNA was isolated and enzymatically hydrolyzed. The hydrolysates were analyzed for 8-OHdG using HPLC with EC detection. PhIP significantly increased the levels of 8-OHdG by 83% after 6 h (P < 0.05), but the increase (47%) at the 24 h point was not significant. p-XSC alone had no effect on the levels of 8-OHdG. However, the elevation of 8-OHdG caused by PhIP at 6 h was significantly inhibited by p-XSC to levels similar to those measured in rats treated with the vehicle only (P < 0.05). p-XSC had no effect on PhIP-induced 8-OHdG at 24 h. I -NP had no effect on the levels of 8-OHdG at either time point. Levels of 8-OHdG were increased by 22% 6 h after DMBA administration and, significantly, rose to 84% at 24 h (P < 0.01); at either time point, this elevation was not inhibited by p-XSC. Although the mechanisms remain to be determined, to our knowledge, this is the first report demonstrating that PhIP and DMBA are capable of enhancing 8-OHdG levels in the rat mammary tissue in vivo.

8-Hydroxy-2'-Deoxyguanosine↗

Fluorous-phase soluble polymeric supports.

Fluorous phase soluble polymer supports derived from fluoroacrylate polymers are described. N-Acryloxysuccinimide-containing fluoroacrylate polymers were readily prepared from commercially available monomers. The activated acrylates so prepared were then converted into chelating and non-chelating ligands by amidation of the N-acryloxysuccinimide active ester residues. Phosphine ligands attached to these supports were used to prepare neutral and cationic rhodium(I) hydrogenation catalysts as well as palladium(0) catalysts. Similar substitution of pendant active ester groups to form hydroxamic acid ligands for metal sequestration is also feasible. Liquid/liquid extraction readily separated, recycled and reused these polymer-bound ligands and catalysts. While fluorous phase solubility could be attained with polymers containing only heptafluorobutyryl groups, selective solubility in a fluorous phase in contact with an organic phase was only seen with fluoroacrylates that contained larger fluorinated ester groups.

Acrylates↗

Analysis of a primer-independent GTF-I from Streptococcus salivarius.

A glucosyltransferase (GTF) gene, designated gtfL, from Streptococcus salivarius was cloned and expressed in Escherichia coli and its nucleotide sequence determined. The GTF-L enzyme catalysed the synthesis of water-insoluble glucan in a primer-independent manner. The nucleotide sequence and derived amino acid sequence of GTF-L were similar in size and domain structure to previously sequenced glucosyltransferases. However, a 464-bp region of high variability was identified which could be selectively amplified from strains of S. salivarius by the polymerase chain reaction and could therefore form the basis for species identification. No sequence-specific motifs related to the solubility and linkage of the glucan product or its need for a dextran primer could be ascertained.

Amino Acid Sequence↗

Nerve growth factor stimulates the tyrosine phosphorylation of MAP2 kinase in PC12 cells.

NGF treatment of PC12 cells results in the rapid activation of MAP2 kinase. We report here that the induction of enzyme activity was correlated with the phosphorylation of MAP2 kinase, detected by metabolic labeling of the enzyme and with anti-phosphotyrosine antibodies. NGF stimulated the phosphorylation of MAP2 kinase on tyrosine, as well as serine and threonine residues. Western blot analysis using a polyclonal anti-phosphotyrosine antibody demonstrated that the tyrosine phosphorylation of MAP2 kinase was maximal within 2 min following NGF exposure and preceded the induction of MAP2 kinase activity. The NGF-stimulated tyrosine phosphorylation of an identified substrate provides direct evidence for the participation of a tyrosine kinase in the mechanism of action of NGF.

Adrenal Gland Neoplasms↗

Universal self-care requisites as identified by homeless elderly men.

1. Given the current economic climate, the number of homeless persons, and the nature of their needs, nurses must be prepared to facilitate movement of all homeless persons toward self-care. 2. Nurses can contribute to the self-care of homeless elderly men by recognizing and eliciting requisites, associated actions, and nursing interventions that reinforce meeting of needs. 3. Study results support Orem's proposition that universal self-care requisites are common to all individuals regardless of age, sex, developmental level, health state, or internal or external conditions. 4. A number of participant's statements used to formulate themes suggested a relationship to more than one category of universal self-care requisites, which suggests that the categories are not mutually exclusive.

Aged↗

Nerve growth factor stimulates the phosphorylation of a 250 kDa cytoskeletal protein in cell-free extracts of PC12 cells.

Nerve growth factor (NGF) rapidly stimulates the phosphorylation of a 250 kDa cytoskeletally-associated protein (pp250) by a protein kinase which is also associated with structural elements of the cell. We have solubilized these proteins and demonstrated that NGF-stimulated phosphorylation can be observed in cell free extracts of cytoskeletons from NGF-treated PC12 cells. The pp250 substrate and the 250-kinase were solubilized from PC12 cytoskeletons by treatment with 2 M urea. Phosphorylation of pp250 was maximally stimulated following treatment of the cells for 5 min with NGF. This effect was transient, diminishing with longer exposure of the cells to hormone. The 250-kinase preferred Mn2+ over Mg2+ and was inhibited by both Na+ and K+. The phosphorylation of pp250 was not affected by Ca2+. Upon fractionation of the urea-soluble cytoskeletal proteins by gel filtration, the 250-kinase eluted in two peaks; one peak of enzyme activity coeluting with the pp250 substrate, and a second peak of enzyme activity eluting with an apparent Mr of approximately 60 kDa. Treatment of the PC12 cells with the phorbol ester TPA also stimulated the phosphorylation of pp250, although this effect was not as great as that produced by NGF. This cell free system should be a valuable tool in the investigation of the mechanisms of NGF action.

Adrenal Gland Neoplasms↗

Association of the epidermal growth factor receptor kinase with the detergent-insoluble cytoskeleton of A431 cells.

The epidermal growth factor receptor (EGF-R) on human epidermoid carcinoma cells, A431, was found to be predominantly associated with the detergent-insoluble cytoskeleton, where it retained both a functional ligand-binding domain and an intrinsic tyrosine kinase activity. The EGF-R was constitutively associated with the A431 cytoskeleton; this association was not a consequence of adventitious binding. The EGF-R was associated with cytoskeletal elements both at the cell surface, within intracellular vesicles mediating the internalization of the hormone-receptor complex, and within lysosomes. The EGF-R became more stably associated with cytoskeletal elements after its internalization. The cytoskeletal association of the EGF-R was partially disrupted on suspension of adherent cells, indicating that alteration of cellular morphology influences the structural association of the EGF-R, and that the EGF-R is not intrinsically insoluble. Cytoskeletons prepared from EGF-treated A431 cells, when incubated with gamma-32P-ATP, demonstrated enhanced autophosphorylation of the EGF-R in situ as well as the phosphorylation of several high molecular weight proteins. In this system, phosphorylation occurs between immobilized kinase and substrate. The EGF-R and several high molecular weight cytoskeletal proteins were phosphorylated on tyrosine residues; two of the latter proteins were phosphorylated transiently as a consequence of EGF action, suggesting that EGF caused the active redistribution of the protein substrates relative to protein kinases. The ability of EGF to stimulate protein phosphorylation in situ required treatment of intact cells at physiological temperatures; addition of EGF directly to cytoskeletons had no effect. These data suggest that the structural association of the EGF-R may play a role in cellular processing of the hormone, as well as in regulation of the EGF-R kinase activity and in specifying its cellular substrates.

Carcinoma, Squamous Cell↗

Wheat germ agglutinin blocks the biological effects of nerve growth factor.

The binding of nerve growth factor (NGF) to specific cell surface receptors initiates a variety of effects that lead to the morphological and biochemical differentiation of clonal pheochromocytoma, PC12, cells. The lectin wheat germ agglutinin (WGA) alters the characteristics of NGF-receptor interaction. We have found that treatment of PC12 cells with WGA dramatically and reversibly inhibits the ability of NGF to elicit three distinct biological effects characteristic of NGF action. Two of these events, the rapid ruffling of cell-surface membranes and the stimulation of the phosphorylation of a 250-kD cytoskeletal protein in situ, occur rapidly and are an immediate consequence of receptor occupancy. Both of these effects are blocked by pretreatment of the cells with WGA. WGA was also found to inhibit the NGF-stimulated regeneration of neurites that occurs over 1-2 d. Both the WGA inhibition of neurite outgrowth and the phosphorylation of the 250-kD cytoskeletal protein were reversed upon addition of the specific sugar N-acetylglucosamine. These data demonstrate that the WGA-induced changes in the NGF-receptor interaction reflect important alterations in the ability of the receptor to transmit biological signals, resulting in the abrogation of the biological effects of NGF on these cells.

Adrenal Gland Neoplasms↗

A marker of human foetal endoderm defined by a monoclonal antibody involves Type 1 blood group chains.

This report demonstrates that a marker of human embryonic endoderm and embryonal carcinoma cells recognized by a hybridoma antibody FC 10.2, involves Type 1 blood group chains with the sequence Gal beta 1 leads to 3G1cNAc beta 1 leads to 3Gal beta 1 leads to 4G1c. This conclusion has been reached from antigenic analyses of meconium, ovarian cyst glycoproteins, oligosaccharides and glycolipids having Type 1 or Type 2 blood group chains. From knowledge of saccharide sequences and blood group related antigens in gastrointestinal tissues of man, we deduce that the 'disappearance' of FC 10.2 antigen from the normal, differentiated cells of the adult may result from masking by additional glycosylations or other substitutions.

Acetylglucosamine↗

A monoclonal antibody marker of human primitive endoderm.

Monoclonal antibodies were raised against the human germ-cell tumor line, LICR LON HT39/7. The cells of this human embryonal carcinoma cell line were first fixed in formol saline and then dehydrated prior to immunization so that antibodies were produced which reacted with antigens surviving conventional histological processing. Eleven hybrid clones secreted antibody that reacted with both formol saline-fixed and living cells of the immunogen. One of these antibodies, LICR LON FC 10.2, has been found to react with a membrane glycoprotein of molecular weight 200,000 restricted in distribution to the surfaces of undifferentiated teratoma-derived cell lines, the luminal surface of human fetal intestine and bronchus and areas of putative endodermal differentiation within germ-cell neoplasms.

Antibodies, Monoclonal↗

Ozone. The good, the bad, and the ugly.

Sensitive individuals are at risk of adverse health effects from exposure to even modest levels of ozone. Such individuals are likely to develop respiratory symptoms and are more likely to be hospitalized when exposed to ozone at currently accepted levels. A review of scientific documents regarding the health effects of ozone has led the DHHS to agree with the EPA that the primary ambient air standard for ozone should be changed from 0.12 ppm (1-hour average) to 0.08 ppm (8-hour average). Achieving the proposed 0.08 ppm standard should decrease physician visits, hospitalization, and use of respiratory medications. In addition, because very susceptible healthy individuals may experience adverse health effects of the current standard, it is clear that the current standard provides little or no margin of safety, particularly for sensitive individuals. In order to avoid exposure to unhealthy levels of ozone, people should take precautions to minimize exposure from 2:00 to 6:00 pm on days when ozone levels are high. This is especially so for children, adults who are active outdoors, those with respiratory disease such as asthma, and people with unusual susceptibility to ozone.

Adult↗