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J Rappaport

Publications and source records attributed to J Rappaport.

At least 55 records · Page 3Linked to original sources
PubMed1995

Assessing the social networks of people with psychiatric disability from multiple perspectives.

The study uses a sample of 97 new members of a mutual-help organization for the seriously mentally ill and 97 of their significant others (61 family members and 36 friends) to examine 1) the degree to which respondents' perceptions of dyadic relationships can be corroborated by network members and 2) the relationship of congruence of perception between respondent-network member pairs, characteristics of respondents' social networks and self-reported symptoms and social adjustment. Results showed strong variability in the degree to which respondents' perceptions were corroborated by network members, with a higher degree of corroboration for factual information such as face-to-face contact than for global aspects of dyadic relationships. Congruence of perception between respondents and family was associated with respondents' feelings of satisfaction about the quality of network ties and better psychological and social functioning. In contrast, congruence of perception between respondents and friends was related to a sense of involvement from ones network, but unrelated to respondents' mental health. The advantages of multiple perspectives data in studying the social ties of people with psychiatric disability are discussed.

Adolescent↗
PubMed1995

Empowerment meets narrative: listening to stories and creating settings.

Comments on and summarizes some of the themes of a special issue on empowerment. Extends empowerment theory with the suggestion that both research and practice would benefit from a narrative approach that links process to practice and attends to the voices of the people of interest. Narrative theory and method tends to open the field to a more inclusive attitude as to what counts as data and to cross-disciplinary insights as well as citizen collaboration. Communal narratives are defined at various levels of analysis, including the community, the organizational, and the cultural. A definition of empowerment that includes a concern with resources calls attention to the fact that communal narratives and personal stories are resources. Implications for personal and social change are suggested.

Community Networks↗
PubMed1995

Transport of phosphorothioate oligonucleotides in kidney: implications for molecular therapy.

The systemic administration of phosphorothioated antisense oligonucleotides has been demonstrated to be an effective strategy for the control of gene expression. Because previous studies have suggested both hepatic and renal accumulation of systemically administered oligonucleotides, we explored whether the kidney might be a site of free DNA transport. [32P]-phosphorothioate oligonucleotides (20 mers) were excreted in urine but cleared at only 30% of glomerular filtration rate. Plasma clearance of the label was very rapid (t1/2 approximately 5 min) but the half life of labeled S-deoxynucleotide excreted in urine was much slower (28 min). Infused oligonucleotide appeared in urine with little degradation. By autoradiography of renal tissue, labeled antisense oligonucleotides appeared within Bowman's capsule and the proximal tubule lumen. DNA was detected in association with brush border membrane and within tubular epithelial cells. Brush border membrane preparations from rat kidney contained oligonucleotide binding proteins as determined by gel mobility shift and UV cross linking assays. Because renal epithelial cells efficiently take up phosphorothioate oligonucleotides without apparent degradation, the kidney appears to be an excellent target for site-directed antisense therapy, but may be a site of antisense toxicity as well.

Animals↗
PubMed1995

Molecular cloning and characterization of a TAR-binding nuclear factor from T cells.

The TAt protein of the human immunodeficiency virus type 1 (HIV-1) activates the expression of viral mRNA through a cis-acting element in the LTR termed TAR. TAR RNA forms a stable stem-loop structure. Mutagenesis studies indicate that the stem structure, the primary sequence of the loop, and three unpaired bases in the stem (bulge) are important for Tat activation. Using the in vitro-transcribed TAR RNA as a probe, we have cloned a gene (TARBP-b) that encodes a TAR-binding protein from a cDNA expression library derived from Hut-78 cells. Expression of the 1.4-kb TARBP-b mRNA was observed in all mammalian cell lines tested. TARBP-b binds specifically to the bulge region of TAR RNA and trans-activates the HIV-1 long terminal repeat in the presence of ptat and prev expression plasmids. These results suggest that TARBP-b contributes to tat-mediated trans-activation.

Amino Acid Sequence↗
PubMed1995

Transgenic models of HIV-1.

Transgenic technology has been very successful at providing insights into possible processes involved in HIV-induced pathogenesis. The availability of these small animal models for the study of HIV-related syndromes including KS, epidermal proliferative lesions, HIV-associated nephropathy, AIDS-related growth failure and cachexia may well facilitate the development of novel therapies for these complications. Other phenotypes created in mice, such as cataracts and hepatic cancer [59], may not have human analogies but may still provide insight into pathogenesis. Thus, transgenic models have already provided resources to study many manifestations of AIDS and others are likely to be developed. The optimal strategy for designing future transgenic animals, however, is less clear. No transgenic mouse model has been generated to date that will provide an avenue for vaccine development. This advance awaits the further discovery of the host factors that facilitate the virus replicative cycle in humans and a better understanding of these pathways in the mouse. For the development of molecular-based therapy, however, the currently available models may well be adequate to test molecular inhibitors of transcription [7,60,61] and post-transcriptional processing of viral mRNA [62]. Whether single or multigenic constructs under the control of the LTR are better or worse for this purpose is a debatable issue. Transgenic technology may yet make an additional contribution to the development of molecular therapy for AIDS. The best method of demonstrating that a gene therapeutic strategy is safe to administer to patients has not been determined. By introducing potentially therapeutic constructs into mice as transgenes, their safety can be assessed in many different cell types in vivo, analogous to toxicological testing in rodents for systemically administered drugs. Thus, transgenic technology has already provided insights into the pathogenesis of HIV-1. While it has not yet proven its utility for vaccine development, transgenic technology holds the promise of being an active participant in the development of both safe and effective gene therapy approaches for the treatment of AIDS.

AIDS Dementia Complex↗
PubMed1994

Patterns of HIV-1 mRNA expression in transgenic mice are tissue-dependent.

To explore tissue-specific factors that may be important in HIV-1 transcriptional and post-transcriptional regulation, we examined a transgenic mouse model containing a mutant provirus deleted in the gag and pol region. The level of transgene expression was tissue-dependent. Skin, muscle, and tail consistently expressed the transgene abundantly; intestine, kidney, and thymus exhibited variable but generally low levels of expression; while liver expression was undetectable by Northern analysis. Individual mRNAs within the family of singly and multiply spliced messages were determined by reverse transcription (rt) of RNA samples from mouse tissues, polymerase chain reaction (PCR) amplification, and Southern hybridization with exon-specific probes. The exact percentage of Tat-coding mRNA that was multiply spliced was also determined by competitive rtPCR. When 2-, 4-, or 7-kb (full-length) mRNA species were calculated as a percentage of the total mRNA, two phenotypes of distribution were detected. Lymphoid tissue (thymus and spleen) and kidney had significantly greater amounts of unspliced message (P < 0.001) regardless of the level of expression. All other tissues expressed the multiply spliced messages encoding Tat, Rev, and Nef predominantly. Furthermore, utilization of the three major second exon splice acceptor sites for tat, rev, and nef was the same in transgenic mice as has been demonstrated in human cells but the splice acceptor site for the vpu/env was different in murine tissue. The marked tissue-dependent patterns of HIV mRNA expression suggest a potential mechanism for the organ-specific manifestations of AIDS.

Alternative Splicing↗
PubMed1994

Negative-strand RNA transcripts are produced in human immunodeficiency virus type 1-infected cells and patients by a novel promoter downregulated by Tat.

Current understanding of human immunodeficiency virus type 1 (HIV-1) transcription is based on unidirectional expression of transcripts with positive-strand polarity from the 5' long terminal repeat. We now report HIV-1 transcripts with negative-strand polarity obtained from acutely and chronically infected cell lines by use of a template orientation-specific reverse transcriptase-PCR assay. These findings were confirmed in natural infection by analysis of RNA derived from peripheral blood mononuclear cell samples from 15 HIV-1-infected patients. A cDNA derived from a 2.3-kb polyadenylated HIV-1 RNA with negative-strand polarity which encodes a highly conserved 189-amino-acid open reading frame antiparallel to the envelope gene was isolated from acutely infected A3.01 cells. Through use of reporter gene constructions, we further found that a novel negative-strand promoter functions within the negative response element of the 3' long terminal repeat, which is downregulated by coexpression of Tat. Site-directed mutagenesis experiments demonstrated that NF-kappa B I and USF sites are crucial for negative-strand promoter activity. These data extend the coding capacity of HIV-1 and suggest a role for antisense regulation of the viral life cycle.

Amino Acid Sequence↗
PubMed1994

Analytic work concerning motherhood.

This paper delineates the intrapsychic development leading up to and during the pregnancy of a patient in her seventh year of analysis who had achieved a comfortable albeit shaky sense of herself. Though many fundamental issues had already been worked through, the miscarriage and the pregnancy, the effect of loss on the one hand and the disequilibrium on the other enabled us to rework connections more affectively and give greater conviction to our work. She clarified and re-established boundaries, thereby moving from the position of being baby to her mother toward the role of providing for her child. In the paper there is some discussion of the maternal ego ideal, its complex formation, and the obstacles in its path. With patients who have a newly acquired sense of themselves, analysis during pregnancy can be invaluable. It enabled this patient to identify in herself what she admired in me in herself, and to believe she could provide for her baby what I had provided for her.

Abortion, Spontaneous↗
PubMed1994

Transcellular activation of the HTLV promoter by human hematopoietic cells.

We examined the ability of hematopoietic cells to transactivate the HTLV promoter by a transcellular mechanism. HeLa cells containing a CAT reporter gene driven by the HTLV-2 promoter were cocultivated with hematopoietic cells of the B-(Raji), T-(HuT78, Jurkat) and monocyte/promyelocytic (THP-1, U937 and HL60) lineages. Cocultivation with U937 and HuT78 cells constitutively and significantly transactivated the HTLV-2 promoter, while no effect was observed with the other lines. However, activation of other T-cell lines (CEM, Jurkat, Molt-3 and MT-4) with a combination of phorbolester and phytohemagglutinin also resulted in potent transactivation. Supernatant from HuT78 cells exhibited detectable transactivating activity, suggesting that the activation is mediated by a secreted factor(s). This factor also transactivates the HTLV-1 promoter. We used a panel of HTLV-1 LTR deletion mutants to map the responsive elements to this factor(s). Unlike the response element to the HTLV transactivator protein, Tax, which can be mapped to a small region in the enhancer, maximal transactivation by the cellular factor(s) required the complete U3 sequence. Transcellular activation of the HTLV promoter by activated T-cells may play a role in the development of leukemia in HTLV infected individuals.

Deltaretrovirus↗
PubMed1993

From the community mental health movement to the war on drugs. A study in the definition of social problems.

In the 1980s, the Reagan and Bush administrations reduced funding for community mental health programs and began instead to support substance abuse treatment agencies. One reason for this shift in policy was that the social problem of mental illness had been captured by progressives in the community mental health movement. Conservatives, therefore, needed a new problem to redefine and use to enact new social control policies. The conservatives' claim that substance abuse is primarily the result of a defect in the character or constitution of the abuser has had profound effects on both social policy and the research community. Greater awareness is needed on the part of researchers as to how social problems have been defined and how government research grants affect our thinking about substance abuse.

Community Mental Health Centers↗
PubMed1992

Inhibition of human immunodeficiency virus type 1 expression by a hairpin ribozyme.

Ribozymes are RNAs that possess the dual properties of RNA sequence-specific recognition, analogous to conventional antisense molecules, and RNA substrate destruction via site-specific cleavage. The cleavage reaction is catalytic in that more than one substrate molecule is processed per ribozyme molecule. We have designed a hairpin ribozyme that cleaves human immunodeficiency virus type 1 (HIV-1) RNA in the leader sequence (at nucleotides +111/112 relative to the transcription initiation site). The ribozyme was tested in vitro and gave efficient and specific cleavage of RNA containing the leader sequence. To test the antiviral efficacy of this ribozyme, we have cotransfected into HeLa cells HIV-1 proviral DNA and a plasmid expressing the ribozyme from the human beta-actin promoter. HIV-1 expression was inhibited as measured by p24 antigen levels and reduced Tat activity. The antiviral effect of the ribozyme appears to be specific and results from directed RNA cleavage; activity requires both a target sequence and a functional RNA catalytic center. These results suggest that this HIV-1-directed hairpin ribozyme may be useful as a therapeutic agent.

Base Sequence↗
PubMed1992

TAR-independent transactivation by Tat in cells derived from the CNS: a novel mechanism of HIV-1 gene regulation.

The Tat protein of human immunodeficiency virus type 1 (HIV-1) is essential for productive infection and is a potential target for antiviral therapy. Tat, a potent activator of HIV-1 gene expression, serves to greatly increase the rate of transcription directed by the viral promoter. This induction, which seems to be an important component in the progression of acquired immune deficiency syndrome (AIDS), may be due to increased transcriptional initiation, increased transcriptional elongation, or a combination of these processes. Much attention has been focused on the interaction of Tat with a specific RNA target termed TAR (transactivation responsive) which is present in the leader sequence of all HIV-1 mRNAs. This interaction is believed to be an important component of the mechanism of transactivation. In this report we demonstrate that in certain CNS-derived cells Tat is capable of activating HIV-1 through a TAR-independent pathway. A Tat-responsive element is found upstream within the viral promoter that in glial-derived cell lines allows transactivation in the absence of TAR. Deletion mapping and hybrid promoter constructs demonstrate that the newly identified Tat-responsive element corresponds to a sequence within the viral long terminal repeat (LTR) previously identified as the HIV-1 enhancer, or NF-kappa B domain. DNA band-shift analysis reveals NF-kappa B binding activity in glial cells that differs from that present in T lymphoid cells. Further, we observe that TAR-deleted mutants of HIV-1 demonstrate normal late gene expression in glial cells as evidenced by syncytia formation and production of viral p24 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Evidence that a sequence similar to TAR is important for induction of the JC virus late promoter by human immunodeficiency virus type 1 Tat.

A specific RNA sequence located in the leader of all human immunodeficiency virus type 1 (HIV-1) mRNAs termed the transactivation response element, or TAR, is a primary target for induction of HIV-1 long terminal repeat activity by the HIV-1-derived trans-regulatory protein, Tat. Human neurotropic virus, JC virus (JCV), a causative agent of the degenerative demyelinating disease progressive multifocal leukoencephalopathy, contains sequences in the 5' end of the late RNA species with an extensive homology to HIV-1 TAR. In this study, we examined the possible role of the JCV-derived TAR-homologous sequence in Tat-mediated activation of the JCV late promoter (Tada et al., Proc. Natl. Acad. Sci. USA 87:3479-3483, 1990). Results from site-directed mutagenesis revealed that critical G residues required for the function of HIV-1 TAR that are conserved in the JCV TAR homolog play an important role in Tat activation of the JCV promoter. In addition, in vivo competition studies suggest that shared regulatory components mediate Tat activation of the JCV late and HIV-1 long terminal repeat promoters. Furthermore, we showed that the JCV-derived TAR sequence behaves in the same way as HIV-1 TAR in response to two distinct Tat mutants, one of which that has no ability to bind to HIV-1 TAR and another that lacks transcriptional activity on a responsive promoter. These results suggest that the TAR homolog of the JCV late promoter is responsive to HIV-1 Tat induction and thus may participate in the overall activation of the JCV late promoter mediated by this transactivation.

Base Sequence↗
PubMed1991

Expansion strategies of a mutual help organization.

Described a study of the expansion strategies of a successful self- and mutual help organization for persons with mental illness. Resource mobilization and behavior-setting theories were used as conceptual frameworks to guide the investigation. Collaborative methods and a grounded theory approach were used. Archives, reports of contacts outside of the organization, and naturalistic observations were data sources. Of particular interest are the processes used by the organization to mobilize internal and external resources and to start new mutual help groups. Results suggest that the organization mobilizes resources from a variety of sources, displays flexibility in securing resources and defining organizational roles, and creates underpopulated settings to encourage individual involvement. The strategies appear to avoid overtaxing resource pools, reduce role ambiguity, and encourage pluralistic participation. Discussion includes several potential explanations for the successful growth of the organization.

Community Mental Health Services↗
PubMed1991

Charting uncharted terrain: a behavioral observation system for mutual help groups.

Describes the development of a behavioral observation system for mutual help meetings and presents evidence supporting its reliability, validity, and utility. The MHOS-BIC (Mutual Help Observation System-Behavioral Interaction Codes) was used by 10 observers to record the sequential flow of group interaction in 527 meetings. Psychometric analyses indicate that the system performed consistently with measurement objectives. Mean kappas for each of the 12 coding categories ranged from .62 to .87; the system demonstrated sensitivity to setting and time differences; and a predictable pattern of correlations was found among BIC categories and conceptually related participant and observer ratings. Studies using the BIC to address substantive questions about mutual help are reviewed, providing further evidence for its validity and utility. An empirical description of mutual help is presented using BIC data, and the promises and limitations of the system are discussed.

Affective Symptoms↗
PubMed1991

Setting phenotypes in a mutual help organization: expanding behavior setting theory.

Expands Barker's theory of behavior settings by proposing an additional method of classifying settings based on their functional/behavioral aspects--the setting phenotype. Although behavior setting theory has been widely hailed as a revolutionary contribution to behavioral science, it has had limited impact on general psychology. This may be due in part to a reliance on a purely structural method of classifying behavior settings--the setting genotype. Behavioral data were collected from 510 meetings of 13 self-help groups from a mutual help organization for persons with problems in living. A cluster analysis was performed to uncover meaningful behavioral patterns among the groups. Four phenotypes were identified: personal, impersonal, small talk, and advising. Mutual help group phenotype was found to be related to a set of setting characteristics as well as to overall rated change of group members. The results are discussed in light of the significance of the phenotype construct for making behavior setting theory more relevant for social scientists.

Activities of Daily Living↗
PubMed1991

HIV-1 infection of human T lymphocytes results in enhanced alpha 5 beta 1 integrin expression.

Altered T cell adherence after human immunodeficiency virus 1 (HIV-1) infection may contribute to viral pathogenesis in the acquired immune deficiency syndrome. To address this hypothesis, we assessed mechanisms of T cell adherence to extracellular matrix proteins in vitro. We found that after HIV-1 infection, both chronically infected H9 CD4+ T cells and acutely infected primary peripheral blood lymphocytes acquired the ability to adhere to the extracellular matrix glycoprotein fibronectin, to a lesser extent to type IV collagen and laminin, but not to type I collagen. H9 cells chronically infected with two of the three HIV-1 strains studied showed approximately a sevenfold increase in attachment to fibronectin, while the same cells infected with the human retrovirus HIV-2 did not. Adhesion was accompanied by changes in morphology, including marked spreading and increased filopodia. These alterations were not blocked by the protein kinase C inhibitor H-7, which did inhibit TPA-induced T cell attachment to fibronectin. Monoclonal antibodies against both the alpha 5 and the beta 1 subunits of the classical fibronectin receptor as well as an Arg-Gly-Asp (RGD) peptide inhibited attachment, whereas anti-alpha 4 monoclonal antibodies and the CS1 peptide did not. Binding to collagen IV was also inhibited by the anti-beta 1 monoclonal antibody, but not the other antibodies. Cells metabolically labeled with [35S]methionine and analyzed by immunoprecipitation with polyclonal anti-beta 1 integrin antibody showed a 2.5-fold increase in integrin synthesis in infected cells compared to uninfected controls. This increase in synthesis was associated with an increase in cell surface expression of both alpha 5 and beta 1 integrins by FACS (registered trademark of Becton Dickinson for a fluorescence-activated cell sorter) analysis. Enhanced expression of integrins such as alpha 5 beta 1 may cause T cell adherence to a variety of tissues, where released viral gene products may induce some of the tissue-specific manifestations of HIV-1 infection.

Amino Acid Sequence↗