In vivo transgenic mutation assays.

Transgenic rodent gene mutation models provide quick and statistically reliable assays for mutations in the DNA from any tissue. For regulatory applications, assays should be based on neutral genes, be generally available in several laboratories, and be readily transferable. Five or fewer repeated treatments are inadequate to conclude that a compound is negative but more than 90 daily treatments may risk complications.

Effect of antagonists for NK(2)and B(2) receptors on antigen-induced airway responses in allergic rabbits.

The effects of the tachykinin NK(2)receptor antagonist, MEN 11420 (300 nmol/kg) and the bradykinin B(2)receptor antagonist, CP 0597 (17.2 and 172 nmol/kg) were studied in a rabbit model of antigen-induced airway responses. Antigen inhalation induced acute bronchoconstriction, airway hyperresponsiveness to histamine, and pulmonary eosinophil infiltration in 3-month-old rabbits immunized with Alternaria tenuis antigen within 24 h of birth.

Differential patterns of executive function in children with attention-deficit hyperactivity disorder according to gender and subtype.

The present investigation examined differential patterns in executive functions of children with attention-deficit hyperactivity disorder (ADHD; no diagnosed comorbid disorders) according to subtype and gender, and identified instrumentation sensitive to executive function in children aged 6 to 12 years with ADHD. Data were obtained from 94 children diagnosed with ADHD (predominantly inattentive, n = 32, ADHD combined, n = 62), and from 28 controls. Participants with ADHD, who were unmedicated at the time of testing, were administered five tests of executive function (the Wisconsin Card Sorting Test, the Stroop Color-Word Test, the Matching Familiar Figures Test, the Trail Making Test, and the Tower of London).

Information resources assessment of a healthcare integrated delivery system.

While clinical healthcare systems may have lagged behind computer applications in other fields in the shift from mainframes to client-server architectures, the rapid deployment of newer applications is closing that gap. Organizations considering the transition to client-server must identify and position themselves to provide the resources necessary to implement and support the infrastructure requirements of client-server architectures and to manage the accelerated complexity at the desktop, including hardware and software deployment, training, and maintenance needs. This paper describes an information resources assessment of the recently aligned Pennsylvania regional Veterans Administration Stars and Stripes Health Network (VISN4), in anticipation of the shift from a predominantly mainframe to a client-server information systems architecture in its well-established VistA clinical information system.

Evidence for the lack of base-change and small-deletion mutation induction by trichloroethylene in lacZ transgenic mice.

Trichloroethylene (TCE) is a widely used industrial solvent employed mainly for degreasing and cold-cleaning metal parts. It is also used for dry cleaning, and in the production of a number of chemical products. It has been shown to induce liver and lung tumors in rodents, and have a variety of positive and negative results using in vitro and in vivo mutagenicity tests.

Vitronectin receptors are expressed by macaque trophoblast cells and play a role in migration and adhesion to endothelium.

The objective of this work was to develop an in vitro system that would extend the usefulness of the macaque as a model for studying trophoblast invasion and spiral artery modification. We sought to determine whether trophoblast cells isolated from early gestation macaque placentas expressed vitronectin receptors and tested the idea that these receptors play a role in trophoblast migration and adhesion. Cytotrophoblast cells were isolated from 40-100 day macaque placentas, cultured, and characterized by immunofluorescence microscopy and flow cytometry.

Transition through stages of smoking: the effect of gender and self-concept on adolescent smoking behavior.

Purpose: To determine whether self-concept, gender, and age are significant factors in an adolescent's transition through stages of smoking to regular smoking.

Methods: A questionnaire composed of 29 items (nine questions pertaining to smoking behavior and 20 to four self-concept variables: physical, family, social, and peer self-concept) was administered to 368 randomly selected high school adolescents (188 males and 180 females) aged 12-17 years during regular contact (roll call) time.

Results: Overall, 40.

Antigen-induced bronchial hyperresponsiveness in the rabbit is not dependent on M(2)-receptor dysfunction.

We have assessed the effect of sensitization to allergen on airway smooth muscle responsiveness and acetylcholine (ACh) release from cholinergic nerves in tracheal preparations from rabbits immunized at birth to Alternaria tenuis and littermate control rabbits injected with saline. ACh release induced by EFS was significantly greater in tracheal preparations obtained from immunized rabbits compared with littermate controls. The ability of the muscarinic-receptor agonist, oxotremorine, to inhibit ACh release to EFS (4 Hz) was not altered by immunization.

The vitronectin receptor plays a role in the adhesion of human cytotrophoblast cells to endothelial cells.

During placental development in higher primates trophoblast cells invade maternal blood vessels and migrate along the luminal surface of endothelium. In the present study, the adherence of human cytotrophoblast cells to endothelial cells has been characterized to test the hypothesis that vitronectin receptors (alpha(v) integrins) play a role in intra-luminal trophoblast migration. Adherence was measured using a quantitative fluorescence-based assay and was found to increase in a time-dependent fashion up to about 2 h after which it leveled off.

Characteristics of 'low risk' and 'high risk' dives by young adults: risk reduction in spinal cord injury.

Study Design: To establish benchmark normative data for dive entries performed by young adults of the age range most likely to sustain a diving spinal cord injury. Data acquired from analysis of the dives performed, along with survey information, were used to determine which factors make the most contribution to the level of risk in diving.

Objectives: To identify influential variables which could contribute to risk of spinal cord injury for each of four types of dives.

Transmission of HIV to the placenta, fetus and mother and implications of gametic infection.

Therapeutic interventions and public education are reducing pediatric AIDS cases in developed countries, but the number of HIV-infected women and children is still a major global concern. The finding that human sperm-associated HIV can be transmitted to oocytes following in vitro fertilization provides a novel viewpoint from which to consider not only the problem of HIV transmission to children but also transmission to women. In the present paper we will first discuss some recent findings that offer new perspectives on the role of the placenta, and particularly the trophoblast, in maternal-fetal transmission of HIV.

Modulation of integrin function inhibits HIV transmission to epithelial cells and fertilization.

Integrin-mediated adhesive interactions are viewed in the context of HIV transmission to susceptible cells and fertilization. The ability of a low-molecular-weight non-peptide integrin modulator to inhibit HIV infection (virus-to-cell and cell-to-cell) and sperm-egg fusion is demonstrated. It is concluded that integrin-modulating substances offer significant promise as female-controlled means for preventing sexual transmission of HIV (whatever entity acts as HIV vector in semen and other penile secretions) and as female-controlled contraceptives.

The relationship between trophoblast differentiation and the production of bioactive hCG.

We previously showed that a significant number of failing pregnancies are associated with production of human chorionic gonadotropin (hCG) having relatively low bioactivity. The present study was designed to compare the secretion of intact, immunoreactive hCG to the secretion of bioactive hCG during trophoblast differentiation, and to test the hypothesis that the lower bioactive: immunoreactive hCG ratios in failing pregnancies are related to reduced or impaired trophoblast differentiation. Cytotrophoblast cells were isolated from term placentas and cultured under conditions that induced or did not induce syncytiotrophoblast formation.

Statistical analysis of lacZ mutant frequency data from MutaMouse mutagenicity assays.

Transgenic mouse assays have provided an unprecedented opportunity to study mutagenesis in diverse rodent tissues. In this article data from MutaMouse mutagenicity assays based on the Escherichia coli gene lacZ were analyzed systematically using liver and bone marrow as potential target tissues. Sources of variation, including plates (within packaging reactions), packaging reactions (within animals) and animals, were evaluated for extra-binomial variation.

Uptake of 125I-labelled alpha2-macroglobulin and albumin by human placental syncytiotrophoblast in vitro.

We have investigated the binding and internalization of alpha2-macroglobulin and serum albumin by human placental syncytiotrophoblast cells in vitro. The time course (obtained at 4 degrees C) of alpha2-macroglobulin binding indicated that an equilibrium was reached after 4 h. The binding of 125I-labelled alpha2-macroglobulin to syncytiotrophoblast cells was competitively reduced in the presence of excess unlabelled alpha2-macroglobulin.

Pathogenetic mechanisms of glaucoma not related to intraocular pressure.

The pathogenesis of the diseases termed open-angle glaucoma remains elusive but progress is being made in understanding more clearly the optic nerve head, vascular, and cellular mechanisms that are associated with them. Even though the greatest risk factors remain intraocular pressure, age, race and refractive error, the association with vascular disease continues to unfold in the literature. Clinical and laboratory studies, although not addressing mechanisms directly as far as we know, continue to probe potential pathways that will ultimately lead to subsets of open-angle glaucoma.

Databases and software for the analysis of mutations in the human p53 gene, human hprt gene and both the lacI and lacZ gene in transgenic rodents.

We have created databases and software applications for the analysis of DNA mutations at the human p53 gene, the human hprt gene and both the rodent transgenic lacI and lacZ loci. The databases themselves are stand-alone dBASE files and the software for analysis of the databases runs on IBM-compatible computers with Microsoft Windows. Each database has a separate software analysis program.

Automated perimetry in detecting threats to fixation.

Purpose: To study in glaucoma patients the threat to fixation on a Humphrey field analyzer program 10-2 when one of the four innermost paracentral points is defective on program 30-2.

Methods: Forty-five eyes of 45 patients with chronic open-angle glaucoma in whom at least one of the innermost four defective paracentral points was reproducibly defective on program 30-2 of the Humphrey perimeter, with a size 3 target, on two consecutive tests, were studied with program 10-2.

Results: Of the 45 eyes with an abnormal paracentral point of program 30-2, 30 (66%) also showed involvement of a paracentral point on program 10-2, which was considered a threat to fixation.

Analysis of tissue-specific lacZ mutations induced by N-nitrosodibenzylamine in transgenic mice.

N-Nitrosodibenzylamine (NDBzA) is a contaminant found frequently in rubber baby bottle nipples and pacifiers. To evaluate more fully the mutagenic potential and analyse the molecular nature of possible mutations induced in vivo, we have studied the mutagenicity of NDBzA in vivo using the MutaMouse system. NDBzA, suspended in olive oil, was administered orally once to male mice at different doses (0, 30, 100, 425 and 750 mg/kg) and the mice were killed 30 and 90 days after treatment.

The effect of 15-HPETE on airway responsiveness and pulmonary cell recruitment in rabbits.

1. In the present study we have investigated the effect of 15-hydroperoxyeicosatetraenoic acid (15-HPETE) and 15-hydroxyeicosatetraenoic acid (15-HETE) on airway responsiveness to inhaled histamine in rabbits in vivo. 2.

The ability of Medmont M600 automated perimetry to detect threats to fixation.

Purpose: The authors studied the sensitivity and specificity of the Medmont M600 central 10 degrees program (Medmont PTY Ltd., Camberwell, Victoria, Australia) in identifying paracentral threats to fixation mapped on the Humphrey program 10-2 (Humphrey Inst. Inc.

Differentiation of human trophoblast cells in vitro is inhibited by dimethylsulfoxide.

Dimethyl sulfoxide (DMSO) exerts a number of biological effects, the most frequently cited being induction of cell differentiation. The compound also increases invasiveness and metastatic potential. In contrast to the many reports of DMSO-induced cell differentiation, we report here that DMSO inhibits the morphological differentiation of human cytotrophoblast cells to syncytiotrophoblast, as revealed by immunofluorescence staining for desmosomal protein and nuclei.

Growth and development of fern gametophytes in an airlift fermenter.

Spores of the fernsPteridium aquilinum andAnemia phyllitidis were grown in an airlift fermenter and subsequent growth and development of gametophytes was monitored. Both species produced greater biomass than that generated in any other solid- or liquid-based culture system tested.Pteridium generated more tissue thanAnemia in every system.

The prevalence and frequency of drug use among Western Australian metropolitan high school students.

Data pertaining to prevalence and frequency of drug use were obtained from 1,394 Western Australian metropolitan high school students using a self-report questionnaire. Alcohol, marijuana, tobacco, hallucinogens, and amphetamines were reported as the most prevalent substances, with over 50% of "current drug users" using alcohol and marijuana on a frequent basis (i.e.