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Biomedical subjects

R Isett

Publications and source records attributed to R Isett.

8 recordsLinked to original sources
PubMed2001

Laminin-5-mediated gene expression in human prostate carcinoma cells.

Interactions between extracellular matrix (ECM) proteins and prostate carcinoma cells provide a dynamic model of prostate tumor progression. Previous work in our laboratory showed that laminin-5, an important member of a family of ECM glycoproteins expressed in the basal lamina, is lost in prostate carcinoma. Moreover, we showed that the receptor for laminin-5, the alpha6beta4 integrin, is altered in prostate tumors. However, the genes that laminin-5 potentially regulates and the significance of its loss of expression in prostate cancer are not known. We selected cDNA microarray as a comprehensive and systematic method for surveying and examining gene expression induced by laminin-5. To establish a definitive role for laminin-5 in prostate tumor progression and understand the significance of its loss of expression, we used a cDNA microarray containing 5289 human genes to detect perturbations of gene expression when DU145 prostate carcinoma cells interacted with purified laminin-5 after 0.5, 6, and 24 h. Triplicate experiments showed modulations of four, 61, and 14 genes at 0.5, 6, and 24 h, respectively. Genes associated with signal transduction, cell adhesion, the cell cycle, and cell structure were identified and validated by northern blot analysis. Protein expression was further assessed by immunohistochemistry. Mol. Carcinog. 30:119-129, 2001.

Blotting, Northern↗
PubMed2001

cDNA microarray analysis of multidrug resistance: doxorubicin selection produces multiple defects in apoptosis signaling pathways.

Doxorubicin plays an important role in the treatment of leukemias, lymphomas, and a variety of carcinomas. Tumor cell resistance to doxorubicin is often associated with expression of the multidrug resistance gene MDR1, which codes for the drug efflux pump P-glycoprotein, and a multidrug-resistant phenotype. Evidence from multiple sources suggests, however, that additional genes besides MDR1 are involved in development of multidrug resistance. To identify genes involved in the multidrug resistance phenotype, we created a 5760-gene cDNA microarray to search for differentially expressed genes between the human multiple myeloma cell line RPMI 8226 and its doxorubicin-selected sublines 8226/Dox6 and 8226/Dox40, both of which express MDR1 and are multidrug-resistant. The cDNA microarray results identified a set of differentially expressed genes, which included MDR1 as expected. Thirty Northern analyses were used to confirm the results of the cDNA microarrays; comparison with the microarray results showed a 90% agreement between the two techniques. Within the set of differentially expressed genes identified by the cDNA microarrays, 29 were of particular interest as they can participate in apoptotic signaling, particularly as mediated by ceramide and the mitochondrial permeability transition. The functional importance of these changes in gene expression is supported by their explanation of the 8226/Dox cell lines' cross-resistance to substances that are not P-glycoprotein substrates, such as Fas/CD95 ligand and staurosporine. We conclude that doxorubicin selection led to changes in gene expression that reduce the apoptotic response to death-inducing stimuli and thus contribute to the multidrug resistance phenotype.

Antibiotics, Antineoplastic↗
PubMed1983

Tolerance for deviance: subjective evaluation of the social validity of the focus of treatment in mental retardation.

Staff members from an American institution, Israeli institutions, and a number of American group homes were asked to rate the social tolerability of 84 types of behavior that reflected either skill deficits or social maladaptation. There was considerable agreement among the three sample groups about the relative rank ordering of the 84 items. Physical violence and socially disgusting behavior were perceived as most intolerable whereas deficits in academic skills were least intolerable. The Israeli sample was uniformly less tolerant than either American sample.

Attitude of Health Personnel↗
PubMed1980

Emotional disturbance in mental retardation: an investigation of differential diagnosis.

The study sought to determine whether 100 emotionally disturbed mentally retarded subjects assigned four distinct diagnostic labels could be differentiated from each other on the basis of sex, age, degree of mental impairment, and adaptive behavior. Univariate and multivariate analyses indicated that the autism classification was distinguishable from psychosis, schizophrenia, and severe emotional disturbance in terms of degree of retardation and adaptive behavior. The primary distinguishing feature was the autistic group's low level of language development. The schizophrenics, psychotics, and severely emotionally disturbed subjects were indistinguishable from each other on the variables examined.

Adolescent↗
PubMed1980

An attempt to assess and predict adaptive behavior of institutionalized mentally retarded clients.

Institutionalized retarded clients (N = 142) were assessed on the Adaptive Behavior Scale (ABS) within 6 months of their admission to Woodhaven Center (Philadelphia) and approximately 12 to 18 months later. While clients were found to progress significantly on 7 of the 10 domains of Part One of the ABS, no significant gains were noted on Part Two. Selected client characteristics (age of admission, sex, IQ, AAMD etiological classification) were also examined as predictors of improvement on the ABS. None of these characteristics was significantly associated with gains on the ABS. The above findings were discussed in terms of specific characteristics of the client population and with respect to limitations of the ABS itself.

Adaptation, Psychological↗
PubMed1979

Services for mentally retarded persons: the viability of a short-term residential service setting in Pennsylvania's system.

Data regarding client discharge and client developmental growth were examined in an attempt to assess the viability of a short-term residential facility within the context of Pennsylvania's service delivery system for mentally retarded persons. While developmental growth was evidenced by all levels of retardation, discharge was notably absent for the profoundly retarded group. A closer examination of the findings highlighted the restraints imposed on the evaluation of a single component of a service system by the larger system in which it operates.

Evaluation Studies as Topic↗