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Biomedical subjects

R L Williams

Publications and source records attributed to R L Williams.

At least 235 records · Page 13Linked to original sources

Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells.

Embryonic stem (ES) cells, the totipotent outgrowths of blastocysts, can be cultured and manipulated in vitro and then returned to the embryonic environment where they develop normally and can contribute to all cell lineages. Maintenance of the stem-cell phenotype in vitro requires the presence of a feeder layer of fibroblasts or of a soluble factor, differentiation inhibitory activity (DIA) produced by a number of sources; in the absence of DIA the ES cells differentiate into a wide variety of cell types. We recently noted several similarities between partially purified DIA and a haemopoietic regulator, myeloid leukaemia inhibitory factor (LIF), a molecule which induces differentiation in M1 myeloid leukaemic cells and which we have recently purified, cloned and characterized. We demonstrate here that purified, recombinant LIF can substitute for DIA in the maintenance of totipotent ES cell lines that retain the potential to form chimaeric mice.

Animals↗

Embryonic lethalities and endothelial tumors in chimeric mice expressing polyoma virus middle T oncogene.

The effect of the middle T oncogene of polyoma virus was studied in vivo using a replication-defective selectable retrovirus. Injection of virus into newborn and adult mice resulted in the rapid appearance of cavernous hemangiomas. Infection of embryos did not yield transgenic mice; therefore, embryonal stem (ES) cells were used as an alternative system. Several infected ES cell clones were established that constitutively expressed middle T and its associated tyrosine kinase activity. Chimeric embryos obtained by blastocyst injection of individual ES cell clones were specifically arrested at midgestation, when multiple hemangiomas disrupted blood vessel formation. From these tumors endothelial cell lines were established that retained expression of von Willebrand factor yet were tumorigenic in vivo. These results suggest that middle T acts in endothelial cells as a single-step oncogene and that ES cells provide a valuable system for the study of growth control during embryogenesis.

Animals↗

Racial differences in neonatal mortality. What causes of death explain the gap?

To examine further the differences in birth-weight-specific neonatal mortality rates between ethnic groups, we studied causes of death for infants of white, black, United States-born Hispanic, and Mexican-born Hispanic women using linked California birth-death records from 1981 to 1983. Black infants of low birth weight had considerably lower neonatal mortality rates from respiratory distress syndrome and congenital abnormalities. In the normal birth-weight category, however, black neonatal mortality rates for most conditions were higher than those for whites. The greatest differences between Mexican-born Hispanic and white neonatal mortality rates were seen for other respiratory conditions and trauma/hypoxia/asphyxia. These differences were most marked in the 1500- to 2499-g and greater than or equal to 2500-g birth-weight categories. Attempts to lower the neonatal mortality rate for black infants of normal birth weight may require providers to focus on both broad preventive measures and improved perinatal management. In contrast, improvements in perinatal management among Mexican-born Hispanics may produce improvement in the neonatal mortality rate for this group.

Black or African American↗

Relationship of locus of control to life style habits.

This study contrasted the life style habits of college students who were high and low on different dimensions of locus of control. The Levenson Locus of Control Scale was used to assess three locus of control dimensions (Internality, Powerful Others, and Chance); the Tennessee Self-Description Form (TSDF) assessed four areas of life-style (Work, Social, Health, and Leisure). High and low groups were formed for each locus of control dimension by taking the top 20% and bottom 20% of the distribution (total N = 162). For all three locus of control variables, a significant interaction was obtained between the high-low group variable and the four areas of life style. The High Internals, Low Powerful Others, and Low Chance groups obtained significantly higher Work and Health scores than did their counterparts.

Adult↗

Albumin adsorption on metal surfaces.

Studies of adsorption kinetics, desorption and adsorption isotherms concerning the interaction between albumin and a range of metal and metal oxides were undertaken in vitro. Three distinct types of behaviour concerning the adsorption of albumin on to metal surfaces were identified. Some metals adsorb considerably greater amounts of protein than might be expected from surface energy alone and it is suggested that electrostatic forces could be responsible for this phenomenon.

Adsorption↗

Electrochemical studies on the influence of proteins on the corrosion of implant alloys.

The effect of proteins on corrosion rates of 316L stainless steel, commercially pure titanium and titanium 6-aluminium 4-vanadium was studied in the static and fretting modes. The static mode was studied using cylindrical specimens as per ASTM F-746, and static fracture fixation plates. The fretting mode was studied using a two-hole plate fretting machine which caused a cyclic rocking motion between the plate and the screws, as per ASTM F-897. Electrochemical techniques of polarization resistance and Tafel slope measurements were used to study effects of proteins on the anodic and cathodic corrosion reactions. It was found that proteins increased the corrosion rate of the stainless steel and C.P. titanium cylindrical specimens, but did not have an effect on the Ti-6AI-4V cylinders. In the fretting mode proteins decreased the corrosion rate of the stainless steel plates, but did not have an appreciable effect on either of the titanium alloys. The presence of proteins appeared to cause an increase in the anodic Tafel constant and a decrease in the cathodic Tafel constant of stainless steel specimens. Significant differences in the shapes of the cathodic Tafel slopes were also seen with cylinders with different surface conditions, and static versus fretting plates.

Alloys↗

Adolescent self-assessment of sexual maturation. Effects of fatness classification and actual sexual maturation stage.

Accuracy of self-assessed staging of sexual maturation was studied on 96 adolescents (49 boys and 47 girls) to validate previous studies and evaluate the effects of an adolescent's fatness level and actual sexual maturation stage on their ability to assess their level of sexual maturation. Correlation between the adolescents' self-assessments and physician assessments was moderately high (Kendall's tau-b = 0.65-0.82). Boys tended to overestimate, while girls underestimated their level of sexual maturation. Differences between physician and subject ratings by fatness classification or by actual sexual maturation stage was not significant. This study supports previous studies showing that adolescents can accurately assess their own stage of sexual maturation regardless of their fatness classification or actual sexual maturation stage.

Adolescent↗

Effect of cimetidine or ranitidine administration on nifedipine pharmacokinetics and pharmacodynamics.

The effect of cimetidine or ranitidine administration on responses to single and multiple doses of nifedipine were studied in 11 subjects who received cimetidine (300 mg q.i.d.) and 12 who received ranitidine (150 mg b.i.d.) in combination with nifedipine. After single doses of nifedipine, cimetidine decreased apparent oral clearance (dose/AUC) from 66 +/- 32 L/hr to 33 +/- 14 L/hr (p less than 0.01); elimination half-life increased from 4.0 +/- 2.2 to 4.9 +/- 2.9 hours (p less than 0.07). Increases in heart rate were greater (26 +/- 13 vs 13 +/- 11 beats/min standing; 19 +/- 11 vs 9 +/- 9 beats/min supine) and lasted longer than after nifedipine alone. Hypotensive effects were similar (10 +/- 7 mm Hg decrease vs 9 +/- 9 mm Hg). During nifedipine multiple-dose administration, cimetidine decreased the apparent oral clearance from 76 +/- 39 to 43 +/- 20 L/hr (p less than 0.01). Blood pressure responses were not altered by cimetidine but heart rate increased more (18 +/- 9 vs 9 +/- 9 beats/min supine; 18 +/- 13 vs 13 +/- 14 beats/min standing). Ranitidine coadministration did not alter nifedipine elimination or dynamic responses. During administration of nifedipine alone, the ratio of oral clearances (multiple to single doses) was 1.1 +/- 0.5. Thus (1) cimetidine but not ranitidine alters responses to nifedipine and (2) nifedipine kinetics do not differ between single- vs multiple-dose conditions.

Adult↗

A selectable temperature-sensitive v-src Moloney retrovirus.

We have cloned the v-src gene of ts339B77 RSV into a new Moloney-based retroviral expression vector (YN). In the resulting construct (ts339YNsrc), the ts339 gene is transcribed from the viral LTR, while a selectable resitance marker, the Tn5 neomycin phosphotransferase (neor) gene, is transcribed from an internal thymidine kinase (Tk) promoter. G418 resistance and focus formation were induced in NIH3T3 cells at comparable efficiencies within the permissive temperature range (33-37 degrees C). At 39 degrees, on the other hand, focus induction was reduced 15-fold with no corresponding decrease in expression of G418 resistance. In cells infected with ts339YNsrc, phosphoproteins were elevated and similar in pattern on SDS PAGE regardless of whether the cells were grown at the permissive or restrictive temperature. The ts339YNsrc virus will be useful for the study of effects of v-src expression, and may also be of help in identifying relevant substrates of the v-src product.

3T3 Cells↗

The crystal structure of ribonuclease B at 2.5-A resolution.

The glycosylated form of bovine pancreatic ribonuclease, RNase B, was crystallized from polyethylene glycol 4000 at low ionic strength in space group C2 with unit cell dimensions of a = 101.81 A, b = 33.36 A, c = 73.60 A, and beta = 90.4 degrees. The crystals, which contained two independent molecules of RNase B as the asymmetric unit, were solved by a combination of multiple isomorphous replacement and molecular replacement approaches. The structures of the two molecules were refined to 2.5-A resolution and a conventional R factor of 0.22 using a constrained-restrained least squares procedure (CORELS). Complexes were also investigated of RNase B plus ruthenium pentaamine and between RNase B and a substrate analogue iodouridine. The polypeptide backbones of the two molecules of RNase B in the asymmetric unit were found to be statistically identical and their differences from RNase A to be statistically insignificant. The carbohydrate chains of both molecules extended into solvent cavities in the crystal lattice and appear to be disordered for the most part. The oligosaccharides appear to exert no influence on the structure of the protein. Iodouridine was observed to bind identically in the pyrimidine site of both RNase B molecules and in a way apparently the same as that previously observed for RNase A. Ruthenium pentaamine bound at histidine 105 of both RNase B molecules in the asymmetric unit, but at a number of secondary sites as well. An array of bound ions was observed by Fo-Fc difference Fourier syntheses. These ions were proximal to lysine and arginine residues at the surface of the proteins while a pair of strong ion binding sites were seen to fall exactly in the active site clefts of both RNase B molecules in the asymmetric unit.

Animals↗

Pharmacokinetics of moricizine HCl.

Moricizine HCl is a phenothiazine derivative with antiarrhythmic properties. It was developed in the USSR and is now undergoing clinical evaluation. Although preliminary work has shown moricizine HCl to be effective in treating both atrial and ventricular arrhythmias, little is known of its pharmacokinetics. There is a 4-fold variability in range for its elimination half-life and in volumes of distribution and clearance. There is a linear relation for peak plasma levels and area under the plasma concentration/time curve with regard to single-dose administration of moricizine HCl. The bioavailability of moricizine HCl connotes extensive first-pass effect, or presystemic metabolism. Very little of moricizine is excreted unchanged; it is extensively metabolized to certain compounds that are present in plasma for extended periods. Moricizine is extensively (92% to 95%) bound to plasma protein. Its coadministration with cimetidine leads to additive systemic effects; however, there is no evidence of alterations in steady-state levels when moricizine HCl is coadministered with digoxin. Because moricizine is a drug with active metabolites, its concentration/effect profile is complex; this poses a challenge for accurate dose titration. This may, however, be a helpful challenge in that the metabolites may one day prove useful in therapy. This surmise warrants further study.

Anti-Arrhythmia Agents↗

Telephone call-in services for children in self-care.

An estimated 8 to 10 million American children younger than 18 years of age are in self-care before or after school. Telephone call-in services to provide adult contact for these children when telephone contact with their parents is impossible or not feasible have been developed in more than 100 cities throughout the country. This study describes 2082 calls received by Tucson's KIDLINE and 2208 calls received by Baltimore's KIDSLINE. The mean age of the callers was 9.7 years, with twice as many girls as boys calling. Loneliness or boredom accounted for 68% of the calls, with fewer calls for help with homework (8%), interpersonal problems (6%), medical problems (3%), and fears (2%). Medical calls were mostly for minor infectious illness; there were no calls for life-threatening emergencies. We discuss the possible implications for pediatric practice.

Adolescent↗

Use of the Eating Attitudes Test and Eating Disorder Inventory in adolescents.

The Eating Attitudes Test and the Eating Disorder Inventory were developed to measure abnormal eating attitudes and behaviors in patients with eating disorders. This report describes each of these self-report questionnaires and outlines their functions, limitations, and previous use with adolescent subjects.

Adolescent↗