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Biomedical subjects

R Lazar

Publications and source records attributed to R Lazar.

26 records · Page 2Linked to original sources
PubMed1982

A search for symmetry in the conditional discriminations of rhesus monkeys, baboons, and children.

Procedures for generating arbitrary matching-to-sample performances may generate only conditional discriminations. Rational grounds for this distinction are proposed, based on the properties that any equivalence relation must possess. Empirical tests are described for determining whether subjects trained on conditional discriminations are also engaged in true matching to sample. A series of studies than leads to the conclusion that proof of true matching to sample by monkeys, pigeons, or baboons is yet to be provided. Whether the absence of such proof reflects experiential factors or species-defined limitations is not presently clear.

Animals↗
PubMed1980

Response of cloned progeny of clinical isolates of herpes simplex virus to human leukocyte interferon.

First- and third-generation cloned progeny viruses were derived from clinical isolates of herpes simplex virus and examined for their sensitivities to human interferon by inhibition of plaque formation in Vero cells. The dose-response curves obtained with the first- and third-generation clones were similar to those obtained with the parental isolates, and both the parent and the clones showed similar sensitivities to interferon. These results suggest that clinical isolates of herpes simplex virus consist of a homogeneous population of virus particles with respect to interferon sensitivity. The dose-response curves obtained with herpes simplex virus demonstrated a shallower slope than those obtained with vesicular stomatitis virus. Vesicular stomatitis virus plaque formation as completely inhibited at high concentrations of interferon, whereas complete inhibition of plaque formation by herpes simplex virus did not occur at the highest concentration of interferon used. Cloned progeny were derived from plaques appearing in the presence of high concentrations of interferon. The dose-response curves and interferon sensitivities of these clones were similar to those of the parent and third-generation clone from which they were derived. There was no evidence for genetic heterogeneity with respect to interferon sensitivity.

Dose-Response Relationship, Drug↗
PubMed1977

Extending sequence-class membership with matching to sample.

Three normal adults were first trained to point sequentially to each member of several pairs of visual stimuli. This baseline training established one class of stimuli to which subjects responded first, and another class of stimuli to which they responded second. Then, in a matching-to-sample procedure, baseline-sequence stimuli served as samples and new visual stimuli served as comparisons. Subjects were trained to choose one group of new comparisons when the sample was a "first" stimulus from the sequence baseline, and to choose the other new comparison stimuli when the sample was a "second" from the sequence baseline. When the new stimuli were then presented as pairs in the posttest, two subjects pointed to them in sequences predictable on the basis of the stimulus-class membership established during matching to sample. The failure of one subject to demonstrate sequential transfer was shown to be a consequence of the failure of the matching-to-sample procedure to establish stimulus classes. The production of sequences that were not directly trained suggested an empirical approach to the analysis of simple grammatical behavior.

Journal Article↗
PubMedDate not supplied

Large-scale manufacturing of safe and efficient retrovirus packaging lines for use in immunotherapy protocols.

BACKGROUND: The use of gene modified T lymphocytes for immunotherapy in a cancer or AIDS clinical trial requires an efficient, safe ex vivo method for modification of these cells at manufacturing scale. Since retroviruses have been shown to be a moderately effective means of stably integrating therapeutic genes into T lymphocytes, we wanted to create packaging and producer cell lines that would produce replication competent retrovirus (RCR)-free supernatants, at large scale (> 200 l), and transduce with high efficiency. METHODS: cDNA expression plasmids containing only coding sequences for gagpol or env were built and sequentially transfected into human 293 cells. Packaging and producer clones were characterized for stability, titer and RCR. A producer clone delivering chimeric immune receptors was scaled-up and supernatants used to transduce patient T lymphocytes for clinical studies. PCR and RT-PCR assays were utilized to evaluate the transmission of HERV-H sequences. Relative infectivity of producer clones pseudotyped with different envelopes was determined by transduction and RT assays. RESULTS: RCR-free, human 293 split-genome packaging lines, pseudotyped with amphotropic, xenotropic, or 10A1 envelopes, were created. A CC49 zeta producer clone was scaled-up to 5 x 54 l lots and supernatants used to safely and efficiently transduce patient T lymphocytes with minimal ex vivo manipulation. While 293 cells express HERV-H mRNA, the transmission frequency in our packaging clones was less than 1 HERV-H sequence per 5 x 10(5) proviral integrations. Additionally, 10A1 and xenotropic packaging lines had higher infectivities than the amphotropic clone. CONCLUSION: These packaging lines represent the safest configuration for the large-scale production of retroviral vectors, and are capable of producing high titer, RCR-free retroviral vector for large scale clinical use. While all three clones efficiently transduce human T lymphocytes, the 10A1 clone has the highest infectivity. These packaging cell lines will be valuable for use in human gene therapy protocols.

Animals↗
PubMedDate not supplied

Biological and physical factors affecting the body burden of organic contaminants in freshwater mussels.

Biological and physical factors affecting the body burdens of hexachlorobenzene, octachlorostyrene, and four polychlorobiphenyl (PCB) congeners in freshwater mussels from Lake St. Clair, Ontario, Canada were investigated. Specimens of Lampsilis radiata (Barnes) and the non-native Elliptio complanata (Lightfoot) were deployed for forty days at four Lake St. Clair sites, to investigate whether the water or the sediment phase represented the primary source of contaminants and to examine the effect of enclosure of the mussels on contaminant uptake. No significant differences in body burdens were detected for any of the compounds between mussels placed in corrals containing uncontaminated sand and those with natural sediment, suggesting the water phase represents the xenobiotic source. Among three enclosure types of varying restriction there were no significant differences in the body burden of each compound indicating the effect of confinement on uptake is minimal. Weak negative correlations between body burden and body length existed for all compounds, although there were no significant differences between the sexes or, with the exception of PCB congener 118, among five indigenous species.

Animals↗