Lack of embryonic homozygous or adult heterozygous lymphatic phenotypes for a Sos1 mutation and lack of lymphatic embryonic phenotypes for a homozygous Cx47 mutation in mice.

We have studied the lymphatic phenotypes of 2 mutations, known to cause abnormalities of lymphatics in humans, in mice. The Cx47 R260C mutation (variably penetrant in humans heterozygous for it and causing limb lymphedema) had an adult mouse phenotype of hyperplasia and increased lymph nodes only in homozygous condition but we did not find any anatomical phenotype in day 16.5 homozygous embryos. Mice harboring the Sos1 mutation E846K (causing Noonan's in man which occasionally shows lymphatic dysplasia) had no adult heterozygous phenotype in lymphatic vessel appearance and drainage (homozygotes are early embryonic lethals) while day 16.5 heterozygous embryos also had no detectable anatomical phenotype.

Additive toxicity of binary mixtures of phototoxic polycyclic aromatic hydrocarbons to the oligochaete Lumbriculus variegatus.

Toxicity of some polycyclic aromatic hydrocarbons (PAHs) can increase by an order of magnitude, or more, in the presence of solar ultraviolet (UV) radiation. In the environment, PAHs exist as complex mixtures, which generally would include multiple PAHs that could cause photoinduced toxicity. Hence, to accurately predict the potential ecological risk of phototoxic PAHs, it is critical to understand their joint toxicity. In this study, we exposed the oligochaete Lumbriculus variegatus to the phototoxic PAHs anthracene, fluoranthene, and pyrene, both singly and as binary mixtures for 96 h. Following this, the animals were exposed to UV light for an additional 96 h, during which periodic observations of mortality were made. Time-dependent phototoxicity of the binary PAH mixtures, expressed as a function of the product of UV light intensity and PAH dose (in the tissue of the animals), was adequately described using a concentration addition model. Given the probability that the PAHs examined acted via a common mechanism of action, this result was consistent with expectations. These data highlight the need to consider the combined photoactivation potential of PAH mixtures and provide the technical basis for a modeling approach to predict their ecological risk.

Retail employees as a group at risk for violence.

Citing studies in which convicted robbers have been interviewed to determine their motives and what factors may have deterred them from committing a planned robbery, the author traces patterns of violence at convenience stores over the past 20 years. She points out that because two thirds of workplace homicides are robbery-related, any efforts to stem the number of robberies will probably also curb the number of homicides.

Auditory vigilance in aphasic individuals: detecting nonlinguistic stimuli with full or divided attention.

Previous research (LaPointe & Erickson, 1991) has shown that aphasic individuals have difficulty, relative to control subjects, in monitoring for spoken words while performing a secondary task. This finding may indicate that aphasics have fundamental deficits in attention or that their linguistic deficits are simply exacerbated by dividing attention. Twenty subjects, 10 nonfluent aphasic and 10 nonaphasic adults, listened to two 10-min series of nonlinguistic acoustic stimuli across conditions of focused and divided attention. Subjects tried to identify target sounds interspersed with nontarget sounds. As in prior research, aphasic subjects performed less accurately on the auditory vigilance task during the divided attention condition, relative to the undivided attention condition and to control subjects. The findings suggest that deficient cognitive processing, intertwined with linguistic deficit, may underlie auditory comprehension deficits in aphasia and may help explain performance variation within aphasic individuals across tasks.

Toxicokinetics and metabolism of aniline and 4-chloroaniline in medaka (Oryzias latipes).

The in vivo toxicokinetics and in vitro hepatic microsomal metabolism of [14C]aniline and [14C]4-chloroaniline in medaka (Oryzias latipes) were investigated to provide a basis upon which to interpret the toxicological responses of small aquarium fish to aniline derivatives. During static aqueous exposures of up to 320 min, parent equivalents failed to reach steady state and results from depuration studies clearly demonstrated biphasic elimination. Due to low elimination rates, 40 to 20% of absorbed aniline and 4-chloroaniline doses, respectively, remained within the fish through 330 min postexposure. Based on an analysis of excreted metabolites, N-acetylation was the dominant route of in vivo metabolism for 4-chloroaniline, with no indication of ring hydroxylation, while the evidence suggested that polar conjugates were the dominant in vivo aniline metabolites. The toxicokinetics and in vivo metabolism of both aniline and 4-chloroaniline were best described by a two-compartment model that was consistent with the assumption that metabolites of the parent amines were accumulating in the fish. In partial support of the hypothesis that these amines are being metabolically activated in medaka, N-hydroxylation of aniline and 4-chloraniline to phenylhydroxylamine and 4-chlorophenylhydroxylamine were quantified in hepatic microsomal preparations.

A physiologically based toxicokinetic model for the uptake and disposition of waterborne organic chemicals in fish.

A physiologically based toxicokinetic model was developed to predict the uptake and disposition of waterborne organic chemicals in fish. The model consists of a set of mass-balance differential equations which describe the time course of chemical concentration within each of five tissue compartments: liver, kidney, fat, and richly perfused and poorly perfused tissue. Model compartmentalization and blood perfusion relationships were designed to reflect the physiology of fishes. Chemical uptake and elimination at the gills were modeled as countercurrent exchange processes, limited by the chemical capacity of blood and water flows. The model was evaluated by exposing rainbow trout (Oncorhynchus mykiss) to pentachloroethane (PCE) in water in fish respirometer-metabolism chambers. Exposure to 1500, 150, or 15 micrograms PCE/liter for 48 hr resulted in corresponding changes in the magnitude of blood concentrations without any change in uptake kinetics. The extraction efficiency for the chemical from water decreased throughout each exposure, declining from 65 to 20% in 48 hr. Extraction efficiency was close to 0% in fish exposed to PCE to near steady state (264 hr), suggesting that very little PCE was eliminated by metabolism or other extrabranchial routes. Parameterized for trout with physiological information from the literature and chemical partitioning estimates obtained in vitro, the model accurately predicted the accumulation of PCE in blood and tissues, and its extraction from inspired water. These results demonstrate the potential utility of this model for use in aquatic toxicology and environmental risk assessment.

Enhancing the social environments of elderly nursing home residents: are high rates of interaction enough?

We investigated the social validity of a common intervention (i.e., serving food during a social hour) that has been reported to facilitate social interaction among nursing home residents. Using a group reversal design, rates of interaction were measured. In addition, the vocal content of the interactions was recorded and coded by raters blind to condition. Rates of interaction more than doubled during the treatment phases, but ineffective vocal behavior accounted for the bulk of the increase. Results suggest the need to examine the utility of such programs in nursing homes.

Isolation and characterization of a polynucleotide phosphorylase from Bacillus amyloliquefaciens.

Bacillus amyloliquefaciens BaM-2 produces large amounts of extracellular enzymes, and the synthesis of these proteins appears to be dependent upon abnormal ribonucleic acid metabolism. A polynucleotide phosphorylase (nucleoside diphosphate:polynucleotide nucleotidyl transferase) was identified, purified, and characterized from this strain. The purification scheme involved cell disruption, phase partitioning, differential (NH4)2SO4 solubilities, agarose gel filtration, and diethylaminoethyl-Sephadex chromatography. The purified enzyme demonstrated the reactions characteristic of polynucleotide phosphorylase: polymerization, phosphorolysis, and inorganic phosphate exchange with the beta-phosphate of a nucleotide diphosphate. The enzyme was apparently primer independent and required a divalent cation. The reactions for the synthesis of the homopolyribonucleotides, (A)n and (G)n, were optimized with respect to pH and divalent cation concentration. The enzyme is sensitive to inhibition by phosphate ion and heparin and is partially inhibited by rifamycin SV and synthetic polynucleotides.

Inhibition of vesicular stomatitis virus replication by poly(2'-fluoro-2'-deoxyuridylic acid).

Poly(2'-fluoro-2'-deoxyuridylic acid) is known to be an effective inhibitor of the deoxyribonucleic acid polymerase found within the oncornaviruses. This synthetic polynucleotide was found to inhibit the replication of vesicular stomatitis virus in mouse L cells. The polymer was shown to be capable of inhibiting the viral ribonucleic acid (RNA)-dependent RNA polymerase, and it is proposed that this is the mechanism of antiviral activity. The following observations support this viewpoint: (i) the polymer is most active when added after virus adsorption; (ii) the antiviral activity is not species specific; and (iii) the polynucleotide is nontoxic to the host cell. Conventional methodologies designed to increase nucleic acid uptake by cultured cells do not show an increase in antiviral potency.

Characterization of a virulent bacteriophage for Bacillus subtilis (var. amyloliquefaciens).

A phage, designated PBA12, has been isolated from the soil and found to be virulent on Bacillus subtilis (var. amyloliquefaciens). PBA12 has a large cylindrical head that is 100 nm long and 35 nm in diameter and a tail that is 200 nm in length. The phage contains double-stranded DNA and demonstrates chloroform sensitivity. The processes of both adsorption and replication appear to be slow and inefficient.

Congression of unlinked markers and genetic mapping in the transformation of Bacillus subtilis 168.

A thorough examination of cotransformation of two unlinked genetic markers in Bacillus subtilis 168 shows that the two recombinational events do not occur randomly. The cotransformation frequency is dependent on the distance between the two markers as well as on the order in which they replicate in the competent cell. These results indicate that uptake and/or integration of DNA molecules bearing these genetic markers is enhanced at the time these markers replicate in the competent cell.

The health care team. The role of pediatric nurse practitioners as viewed by California pediatricians.

A single-mailing questionnaire surveyed attitudes of members of District IX, American Academy of Pediatrics (California) toward the role of the pediatric nurse practitioner (pnp). Responses from 568 members (53%) represented a broad range of age, practice type (58% group, 25% solo, 17% "other"), geographic location, and opinion. The most favorable attitudes toward pnp use were expressed by young pediatricians in large-group and "other" categories; least favorable were solo practitioners older than 60 years. Practice type was more important than age. Most respondents expressed the opinion that a pediatrician-pnp team approach would enrich both professions, and that parental acceptance of the pnp was likely; but that pnp use would not reduce costs. Majorities favored the concept of the pnp as part of the practice team but under constant pediatrician surveillance: seeing the patient for part of the visit and participating under supervision in care for minor illness, but not replacing the pediatrician even in well-child care. Some pnps hope for a more independent role on the pediatrician-pnp team. Modification of both pediatrician and pnp ideas appears requisite to a team approach that will satisfy both professional groups and the public.

Structure and replication of chromosomes in competent cells of Bacillus subtilis.

Competent cultures of Bacillus subtilis 168 were fractionated on gradients of Renografin-76 to obtain a population enriched for competent cells. The cells in this fraction contained two nuclear bodies. The competent cell fraction synthesized deoxyribonucleic acid and ribonucleic acid at reduced rates compared to the noncompetent cell fraction and appeared to divide synchronously upon incubation. The state of the chromosome in competent cells was determined by density transfer experiments and marker frequency analyses. The results are consistent with a competent cell possessing two, or a multiple of two, chromosomes, one complete and the other partially duplicated. During subsequent growth the partially completed chromosome replicates preferentially.