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Biomedical subjects

L Collins

Publications and source records attributed to L Collins.

At least 91 records · Page 5Linked to original sources

Structure-function analysis of human interleukin-2. Identification of amino acid residues required for biological activity.

To locate functional domains of the interleukin-2 (IL-2) protein, a cDNA clone encoding biologically active human IL-2 was mutagenized using synthetic oligonucleotides to incorporate defined amino acid substitutions and deletions in the mature protein. The IL-2 analogs were then produced in Escherichia coli and assayed for the ability to induce proliferation of IL-2-dependent cells and the ability to compete for binding to the IL-2 receptor. Our analysis of over 50 different mutations demonstrated that the integrity of at least three regions of the IL-2 molecule is required for full biological activity: the NH2 terminus (residues 1-20), the COOH terminus (residues 121-133), and 2 of the 3 cysteine residues (58 and 105). Deletion of the NH2-terminal 20 amino acids or the COOH-terminal 10 amino acids resulted in the loss of greater than 99% of bioactivity and binding. Amino acid substitutions at specific positions in these regions also resulted in proteins which retained less than 1% activity. The NH2 terminus and an adjacent internal region were recognized by neutralizing anti-IL-2 antibodies. In combination with the results from epitope competition analysis with neutralizing antibodies, these data are consistent with the IL-2 protein being folded such that the NH2 terminus, the COOH terminus, and the internal 30- to 60-region are juxtaposed to form the binding site recognized by the IL-2 receptor.

Amino Acid Sequence↗

Time series analyses of respiratory responses to indoor and outdoor environmental phenomena.

A time series analysis was utilized to evaluate respiratory responses to outdoor and indoor air pollutant and aeroallergen exposures in potentially sensitive adults in a dry arid environment. Daily symptoms and peak flows were recorded in populations of asthmatics, allergic individuals, those with chronic lung disease symptoms, and asymptomatic individuals (total sample size of 204) over a period of a few years. Meteorology and ambient pollutant concentrations were measured in the basin. Indoor pollutant measurements were made for particulates and CO, indicating that gas stoves and tobacco smoking were the predominant indoor sources. Time series analysis helped determine appropriate lags between environmental stimuli and health responses. Asthmatics showed that most respiratory responses while asymptomatics showed no significant responses. Outdoor ozone, nitrogen dioxide, aeroallergens and meteorology, and indoor gas stoves were significantly related, independently and interactively, with symptoms and peak flow.

Air Pollutants↗

Generation of purified stromal cell cultures that support lymphoid and myeloid precursors.

Treatment of Dexter-type long-term bone marrow cultures with the antibiotic mycophenolic acid (MPA) eliminates all hemopoietic cells from the cultures, while a morphologically intact, adherent stromal cell layer is retained. The ability of these MPA treated stromal cell cultures to support long-term hemopoiesis was tested by seeding them with fresh bone marrow cells that had been passed through nylon wool. This procedure yields a relatively stromal cell depleted population of hemopoietic cells. An aliquot of 5 X 10(5) or 2.5 X 10(5) nylon wool passed bone marrow cells bearing the T6 chromosomal marker was seeded onto replicate MPA-treated stromal cell layers. The stromal cells stimulated the proliferation of the bone marrow cells, and nonadherent cells were present for up to 8 weeks of culture. Progenitors of granulocytes and macrophages (CFU-GM) were also present for this period of time despite weekly demi-depopulation, during culture feeding. Karyotypic analysis confirmed that the CFU-GM were derived from the reseeded population. Nylon wool-passed bone marrow cells seeded alone into empty flasks under identical conditions did not survive past 1 week. Cells from the reseeded cultures were also tested for early myeloid precursors (CFU-S) and injected into immunodeficient CBA/N mice to test for the presence of primitive B cell precursors. CFU-S were present in mice killed 11 days following injection of cells, and high levels of B cell colony-forming units (CFU-B) were present in mice 4 weeks post reconstitution. Further studies demonstrated that factors present in medium conditioned by the stromal cells could support the growth of CFU-GM. These data indicate that treatment of long-term bone marrow cultures with MPA results in a population of functional stromal cells.

Animals↗

Parelaphostrongylus tenuis in captive reindeer and sable antelope.

Parelaphostrongylus tenuis caused neurologic disease in 6 reindeer (Rangifer tarandus tarandus) and 2 sable antelope (Hippotragus niger) that were housed at the National Zoological Park Conservation and Research Center in Front Royal, Va. Progressive hindlimb ataxia and weakness were seen in all affected animals. The parasite was recovered from the subdural space of one reindeer and was seen histologically within the neuropil of another reindeer and a sable antelope. In the other reindeer and sable antelope, diagnoses of parelaphostrongylosis were based on clinicoepidemiologic findings and microscopic lesions. Because parelaphostrongylosis is a density-dependent disease and because the number of white-tailed deer probably will increase, the incidence of P tenuis infections in domestic and nondomestic animals probably will increase as well. Zoos and wildlife parks especially should be cautious when introducing exotic hoofstock to areas with Parelaphostrongylus tenuis-infected white-tailed deer.

Animals↗

Fetal umbilical artery flow velocity waveforms and placental resistance: clinical significance.

Since the umbilical arteries carry fetal blood to the placenta we studied flow velocity waveforms in these vessels with a simple continuous wave Doppler system to assess placental blood flow. The ratio of peak systolic to least diastolic (A/B) flow velocity was measured as an index of placental flow resistance. In 15 normal pregnancies there was a small but significant decrease in this ratio through the last trimester. The A/B ratio was measured on 436 occasions in 168 high-risk pregnancies. In 32 of 43 fetuses subsequently shown to be small for gestational age there was an increase in placental flow resistance with reduced, absent or even reversed flow in diastole. This finding was also present in the one fetus which died in utero. Serial studies in patients with fetal compromise indicated increasing flow resistance, a reverse of the normal trend. These results were not available to the clinician yet of 24 fetuses born before 32 weeks 13 had a high A/B ratio, and all of them were born electively. Maternal hypertension was associated with an increase in fetal placental flow resistance. The umbilical artery A/B ratio provides a new and non-invasive measure of feto-placental blood flow resistance.

Adult↗

Total and regional lung retention of monodisperse cobalt compound aerosols after a single inhalation.

After a single short term inhalation of monodisperse cobalt compound aerosols with preselected physical and chemical parameters the long term retention in beagle dogs is determined measuring their radioactive Co-57 label by a gamma camera. Additionally the major clearance pathways are estimated by excretion analyses. The biological variability of the lung retention is small but it depends clearly on the physiochemical properties of the inhaled aerosol particles. The predominant clearance mechanism in the lung is a moderate dissolution process depending on the specific surface area of the particles. So cobalt oxide particles with an adjustable solubility in the lung can be used for studies of distinct dissolution processes in the lung. Using a gamma camera the dynamics of particle accumulation in the tracheobronchial lymph nodes and the subsequent clearance are analysed on single dogs.

Aerosols↗

A comparison of children who receive and who do not receive permission to participate in research.

In a study examining children's social competence in elementary school settings, the authors had the opportunity to compare children who received parental permission to participate to children who did not receive permission. Results indicated that children who were not involved in the study were more likely to be viewed by teachers as having unsatisfactory relationships with peers than children who were in the study. The present results suggest that investigators begin reporting the number of children who do not participate in a given study and begin examining whether minors who receive parental permission differ on important dimensions from minors who do not receive such permission. Ethical considerations of the present study are discussed.

Behavioral Research↗

The envelope gene and long terminal repeat sequences contribute to the pathogenic phenotype of helper-independent Friend viruses.

Friend murine leukemia virus (F-MuLV) and Friend mink cell focus-inducing virus (Fr-MCF) are helper-independent murine retroviruses which induce a rapidly fatal erytholeukemia in NIH Swiss mice. Amphotropic clone 4070 (Ampho) is a murine retrovirus which does not cause leukemia in these animals. Mice inoculated with Ampho, an Fr-MCF/Ampho pseudotype, or F-MuLV developed leukemia in 0, 50, and 100% of animals, respectively. To identify the F-MuLV and Fr-MCF sequences responsible for leukemia, we constructed hybrid viral genomes between these viruses and Ampho, using subgenomic fragments of molecularly cloned viral DNA. Transfection of these hybrid viral DNAs into fibroblasts produces recombinant retroviruses. These new viruses are assayed in vivo for their ability to cause leukemia. Recombinant viruses constructed between the Ampho genome and the Fr-MCF envelope gene do not cause leukemia. Similarly, viruses constructed by using either the Fr-MCF long terminal repeat U3 region or the F-MuLV long terminal repeat U3 region and the remainder of the Ampho genome do not cause leukemia. However, if the Fr-MCF envelope gene plus the Fr-MCF U3 region are joined to Ampho, the resulting virus causes erythroleukemia in 14% of mice. Recombinant viruses made between the Fr-MCF envelope gene, the F-MuLV U3 region, and the remainder of the Ampho genome cause erythroleukemia in 38% of mice. This study demonstrates that both the envelope gene of Fr-MCF and the U3 regions of Fr-MCF and F-MuLV contain sequences which contribute to the leukemic phenotype of helper-independent Friend viruses.

Animals↗

Molecular cloning of Friend mink cell focus-inducing virus: identification of mink cell focus-inducing virus-like messages in normal and transformed cells.

Friend mink cell focus-inducing virus (Fr-MCF) is a leukemogenic murine retrovirus that was isolated from a leukemic NIH Swiss mouse. We molecularly cloned the genome of this virus into pBR322. Restriction enzyme mapping of this cloned Fr-MCF DNA revealed a 1.0-kilobase-pair region in the envelope gene which differs from the restriction map of the Friend ecotropic virus (Friend murine leukemia virus). A 400-base-pair Fr-MCF envelope gene fragment was subcloned from this region and designated pLEK. Probes made with pLEK hybridize to Fr-MCF DNA but do not hybridize to either Friend or amphotropic murine leukemia virus DNA. Polyadenylic acid-selected RNA was prepared from the hematopoietic tissues of normal NIH Swiss mice, Fr-MCF-infected erythroleukemia cells (TP-1), and uninfected chemically transformed T lymphocytes (RB-1). The pLEK probe identified 34S and 22S messages in the TP-1 cells and in the normal hematopoietic tissues. RB-1 cells contain 32S and 26S messages that hybridize to pLEK. However, the pLEK-like RNAs found in the normal hematopoietic tissues and in the RB-1 cells were 400-fold less abundant than the RNAs found in the TP-1 cells.

Animals↗

Survey of operating room pollution within an N.H.S. district.

Pollution by waste anaesthetic gases was measured in all operating departments in a typical N.H.S. district. Methods were chosen to provide time-weighted average levels over the period of each operating session. The results showed that air-conditioning alone could not guarantee pollution levels below suggested maximum levels and that to meet those requirements air-conditioning plus scavenging was necessary. Background pollution levels were found to be representative of the personal exposure of nursing staff but approximated to only one third of the anaesthetists' personal exposure. Dental clinics presented special problems, namely the very high levels of pollution to which the dentist and his assistants were exposed.

Air Conditioning↗

Attributional and behavioral changes following two behavior management interventions with hyperactive boys: a follow-up study.

In a 6-month follow-up study of 2 interventions with hyperactive boys, different patterns of improvement were observed for an intervention which focused on self-control and 1 which employed contingent social reinforcement. Of the 2 manipulations, self-control methods produced significantly stronger long-term benefits in terms of the child's increased perception of personal control over academic outcomes; social reinforcement, on the other hand, produced significantly stronger long-term benefits in terms of teacher ratings of hyperactivity or impulsivity (Conners Teacher Rating Scale). Both interventions produced stable changes in terms of decreased behavioral impulsivity as measured by qualitative error scores on the Porteus Mazes.

Achievement↗

Q- and C-bands in the metaphase chromosomes of Drosophila nasutoides.

The large heterochromatic chromosome of Drosophila nasutoides reveals distinctive C- and Q-bands. The regions which are negative in C-banding appear positive in Q-banding. The isochromosomic nature of this chromosome and the locality of the satellite DNAs in this chromosome are discussed with respect to these banding patterns.

Animals↗