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PubMed2001

Senescence represses the nuclear localization of the serum response factor and differentiation regulates its nuclear localization with lineage specificity.

The differentiation of cultured 3T3T mesenchymal stem cells into adipocytes represses growth factor responsiveness by limiting the nuclear localization of the serum response factor (SRF) that binds to and activates the promoters of growth control genes that contain the serum response elements (SRE), such as junB and c-fos. The regulation of SRF nuclear localization by adipocyte differentiation is specific, because we show that adipocyte differentiation does not repress the nuclear localization of six other transacting factors. To determine if repression of growth factor responsiveness that occurs during senescence also represses the nuclear localization of SRF, we studied normal human WI-38 fibroblasts at low versus high population doublings. The results show that SRF localizes to the nucleus of proliferative cells whereas in senescent cells SRF can not be detected in the nucleus. This result is apparent in both immunofluorescence assays and in western blot analysis. We next evaluated the cellular distribution of SRF in selected human tissues to determine whether the loss of proliferative potential in vivo could have a different effect on SRF nuclear localization. We found that in cells of the small bowel mucosa, differentiation modulates SRF nuclear localization in an opposite manner. Minimal SRF expression and nuclear localization is evident in undifferentiated cells at the base of crypts whereas increased SRF expression and nuclear localization is evident in differentiated cells at the surface tip of the villus. These results together establish that regulation of SRF expression and nuclear localization is important in senescence and differentiation in a lineage specific manner.

Adipocytes↗
PubMed1984

The dynamics of interorganizational coordination.

A theory was developed on the creation, growth, and decline of relationships among organizations and was tested, using a longitudinal study of 95 dyadic relationships among child care and health organizations in Texas. Using LISREL V, the test of the theory showed that substantial revision of the model was required to explain the data adequately. When the model was revised, important new patterns were revealed in the development of interorganizational relationships over time: (1) Perceptions of dependence on others for resources spurs the development of interorganizational relationships. Resource dependence is a powerful direct determinant of communications, resource transactions, and consensus; (2) The growth of interorganizational relationships is fostered by frequent communications to formalize the relationship and build consensus about the terms of the relationship among the parties involved; (3) Monetary transactions and client referrals entail different patterns of coordination; and (4) Consensus among parties in an interorganizational relationship is both a positive outcome of initial resource dependence and communications and has a negative influence on subsequent perceptions of resource dependence.

Analysis of Variance↗
PubMed1991

Mental health, social relations, and social selection: a longitudinal analysis.

A wide body of literature documents the effect of social networks and social supports on mental health. Fewer studies, however, have examined the reciprocal effect of mental health on social relationships. This problem is examined using data from a national panel survey of adults aged 20-64. For the sample as a whole, support was found for a social selection process, since psychological distress predicted decreases in primary, but not secondary, social relationships. The extent of primary relationships also were found to be associated with subsequent distress, providing evidence that the relationship between mental health and social environment may be transactional. When examined separately by gender, males but not females were found to be vulnerable to the process of social selection, supporting the hypothesis that the expression of distress is less role-appropriate for men and therefore more likely to invite social sanctions. Social causation effects also were observed only among males.

Adult↗
PubMed1995

The measurement of social support in the 'European Research on Incapacitating Diseases and Social Support': the development of the Social Support Questionnaire for Transactions (SSQT).

Social support is supposed to have a beneficial effect on the health and wellbeing of people. It is a central concept in the 'EUropean Research on Incapacitating DIseases and Social Support' (EURIDISS). In general, two main distinctions concerning social support are made in the literature, providing four basic dimensions or types of social support: a social-emotional vs an instrumental type of social support, and a 'crisis' or 'problem-oriented' vs 'everyday' or 'daily' type of social support. Based on these types of social support, a series of items were formulated to measure actual supportive interactions or exchanges of resources. The items were spread over five scales. The social-emotional type of social support comprised three scales: daily emotional support; problem-oriented emotional support; and social companionship, while the instrumental type of social support consisted of two scales: the daily instrumental support and the problem-oriented instrumental support. Together, these items and scales constitute the so-called 'Social Support Questionnaire for Transactions' (SSQT). The main objective of this paper is to investigate whether one and the same instrument, i.e. the SSQT, allows for meaningful comparisons between patients with rheumatoid arthritis from different countries. More specifically, the dimensionality and invariance of the dimensions across countries of the SSQT are explored. To this end, patients from four different European countries (France, Norway, The Netherlands and Sweden) were asked to fill in the SSQT. The analysis of the data using principal component analysis (PCA) and simultaneous component analysis (SCA), did yield the intended scales, although the internal consistency of one of them, the daily instrumental support scale, is questionable.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗
PubMed1998

Imprinting mechanisms in mammals.

Imprinting is a genetic mechanism that determines expression or repression of genes according to their parental origin. Some imprinted genes occur in clusters in the genome. Recent work using transgenic mice shows that multiple cis-acting sequences are needed for correct imprinting. Mutation analysis in a normal chromosomal context reveals the importance of imprinting centres for regional establishment or maintenance of imprinting in a cluster. Elements that contribute to the function of imprinting centres and regional propagation of the imprints are CpG-rich differentially methylated regions (that during development retain germline imposed methylation or demethylation), direct repeat clusters, and unusual RNAs (antisense, non-translated etc.). The interaction of these cis elements with transacting factors such as methylase and chromatin factors establishes a hierarchical control system with local and regional effects.

Alleles↗
PubMed1998

Translational control elements in the major human transforming growth factor-beta 1 mRNA.

Polysome analysis indicates that the major 2.4 kb transforming growth factor-beta 1 (TGF-beta 1) transcript is poorly translated, both in cultured cells, and in vivo in mouse liver. In contrast, the TGF-beta 2 transcripts are efficiently translated. The contribution of the 5'- and 3'-untranslated regions (UTRs) to the translational inhibition of the full-length TGF-beta 1 transcript was studied by deletion analysis. Despite their high G + C content, both UTRs stimulated translation in vitro. However, polysome analysis of synthetic TGF-beta 1 mRNAs transfected into MCF-7 cells suggests that the cell contains a limited pool of trans-acting factors that interact with the 5'UTR to make it inhibitory in vivo. Further deletion analysis in vitro revealed multiple stimulatory and inhibitory regions in the 5'UTR. This has important implications for the translatability of the naturally occurring shorter TGF-beta 1 transcripts and provides a framework for higher resolution mapping studies. Overall, the poor translational efficiency of the major TGF-beta 1 mRNA in vivo appears to be due to a combination of poor initiation sequence context, and inhibitory interactions of limiting transacting factors with cis-inhibitory elements embedded in an otherwise stimulatory 5'UTR.

3' Untranslated Regions↗
PubMed2003

The Enterococcus hirae paradigm of copper homeostasis: copper chaperone turnover, interactions, and transactions.

The cop operon is a key element of copper homeostasis in Enterococcus hirae. It encodes two copper ATPases, CopA and CopB, the CopY repressor, and the CopZ metallochaperone. The cop operon is induced by copper, which allows uncompromised growth in up to 5 mM ambient copper. Copper uptake appears to be accomplished by the CopA ATPase, a member of the heavy metal CPx-type ATPases and closely related to the human Menkes and Wilson ATPases. The related CopB ATPase extrudes copper when it reaches toxic levels. Intracellular copper routing is accomplished by the CopZ copper chaperone. Using surface plasmon resonance analysis, it was demonstrated that CopZ interacts with the CopA ATPase where it probably becomes copper loaded. CopZ in turn can donate copper to the copper responsive repressor CopY, thereby releasing it from DNA. In high copper, CopZ is proteolyzed. Cell extracts were found to contain a copper activated proteolytic activity that degrades CopZ in vitro. This post-translational control of CopZ expression presumably serves to avoid the accumulation of detrimental Cu-CopZ levels.

Adenosine Triphosphatases↗
PubMed1994

What brings about change in psychoanalytic treatment?

The development of two general points of view regarding what brings about change in psychoanalytic treatment is traced in this article. One set of conceptions emphasizes interpretation, especially of the transference, and historical or narrative reconstruction. The other set emphasizes the experiential and transactional aspects of a new and better human relationship. Various current versions of this difference in emphasis are discussed. Future investigation is needed to distinguish the role of correction of expectations generated out of actual infantile experiences through the new relationship to the analyst, from the role of interpretation of early fantasy activity and reconstruction of how this was generated and congealed in the patient's childhood. The danger of avoiding the analysis of core infantile fantasy activity and its effect on the patient's current perception, thinking, and behavior, by a premature termination of the treatment when the relationships of the patient seem to be more successful, mature, and realistic, is stressed. One must be careful not to utilize self psychology or object relations theory beyond foundational repair in psychoanalytic therapy without considering the consequences. One must ask oneself always if one is utilizing such theories and practices and the interpretations based on them defensively, in a collusion to avoid facing the patient's core unique childhood oedipal and preoedipal fantasy activity and the reverberations of it in the analyst's core fantasy activity. Continuing self-analysis is required in each and every treatment process, which is why the analyst also learns and matures from every case. The openness of the analyst permits insight through interpretation, meliorative noninterpretive aspects of the new object relationship or experience, regression due to the analyst's reliability which gives the opportunity to undo developmental arrests through the analysis of core fantasies, a symbolic holding environment, and the collaborative creation of a narrative, all of which are known to have therapeutic effects and work together to produce change in psychoanalytic treatment.

Fantasy↗
PubMed2001

An analysis of the effects of depth-dependent aggregate modulus on articular cartilage stress-relaxation behavior in compression.

An accurate description of the mechanical environment around chondrocytes embedded within their dense extracellular matrix (ECM) is essential for the study of mechano-signal transduction mechanism(s) in explant experiments. New methods have been developed to determine the inhomogeneous strain distribution throughout the depth of the ECM during compression (Schinagl et al., 1996, Annals of Biomedical Engineering 24, 500-512; Schinagl et al 1997. Journal of Orthopaedics Research 15, 499-506) and the corresponding depth-dependent aggregate modulus distribution (Wang and Mow, 1998. Transactions of the Orthopaedics Research Society 23, 484; Chen and Sah, 1999. Transactions of the Orthopaedics Research Society 24, 635). These results provide the motivation for the current investigation to assess the influence of tissue inhomogeneity on the chondrocyte milieu in situ, e.g. stress, strain, fluid velocity and pressure fields within articular cartilage. To describe this inhomogeneity, we adopted the finite deformation biphasic constitutive law developed by Holmes and Mow (1990 Journal of Biomechanics 23, 1145-1156). Our calculations show that the mechanical environment inside an inhomogeneous tissue differs significantly from that inside a homogeneous tissue. Furthermore, our results indicate that the need to incorporate an inhomogeneous aggregate modulus. or an anisotropy, into the biphasic theory to describe articular cartilage depends largely on the motivation for the study.

Cartilage, Articular↗
PubMedDate not supplied

Vulnerability and sexual risks: Vagos and vaguitas in a low income town in Perú.

Young people constitute a priority for sexual health research, policy and planning. Many studies, however, regard youth as a homogeneous group defined by developmental stages and their problems as inherent rather than factors resulting from structural vulnerability. Ethnographic data from this study provided strong evidence of the inappropriateness, in prevention interventions, of the concept of 'young people' as a group defined only by age and gender. When incorporating social resources and support into the analysis, specific segments of youth with diverse sexual practices and health seeking behaviours emerge. Thus, although most young people in urban areas show a similar level of HIV/STI knowledge, their exposure to risk varies according to their living conditions. Two population segments - "street guys" and "fast girls" - identified as vulnerable for sexual risk, are characterized. Both groups hang out on the streets, and most are involved in using alcohol and drugs, and/or practicing transactional sex. This study provided evidence for the need of various approaches according to level of poverty and social vulnerability in order to develop more effective HIV/AIDS and STI prevention programs to meet the needs of young men and women in low-income areas.

Adult↗
PubMed2006

A comparison of alternative strategies for cost-effective water quality management in lakes.

Roughly 45% of the assessed lakes in the United States are impaired for one or more reasons. Eutrophication due to excess phosphorus loading is common in many impaired lakes. Various strategies are available to lake residents for addressing declining lake water quality, including septic system upgrades and establishing riparian buffers. This study examines 25 lakes to determine whether septic upgrades or riparian buffers are a more cost-effective strategy to meet a phosphorus reduction target. We find that riparian buffers are the more cost-effective strategy in every case but one. Large transaction costs associated with the negotiation and monitoring of riparian buffers, however, may be prohibiting lake residents from implementing the most cost-effective strategy.

Agriculture↗
PubMed1987

The measurement of hospital efficiency.

The measurement of efficiency in the hospital sector is particularly difficult given that there is no universally recognised objective function. A generalised neo-classical approach is adopted in specifying a hospital objective function which acknowledges the importance of transaction costs and property right holdings in this sector. It is shown that such an approach may be used to distinguish between technical and allocative efficiency, thereby aiding interpretation of the stochastic element contained in production models. Quantification of allocative inefficiency is also undertaken.

Cost-Benefit Analysis↗
PubMed1964

INTERLIBRARY LOAN, 1952-62: TEN YEARS OF PROGRESS?

Although the revised General Interlibrary Loan Code of 1952 was designed to alleviate the "crisis" in interlibrary loan services existing at the time, libraries today find that they are still facing the same problems as they did in 1952, namely, excessive use of large, distant libraries for materials available locally, unverified references, stringent restrictions on the materials lent and their subsequent use, and the rising cost of operating interlibrary loan programs. A brief description of the use and abuse of interlibrary loans at the National Library of Medicine is followed by consideration of the alternatives to the concept of interlibrary loan presently under study in various regions. To relieve the current situation, it is proposed that federal funds be made available to medical and scientific libraries on the basis of the percentage of interlibrary loan transactions handled (2 percent of their total circulation figure), that present lending restrictions on materials be relaxed, that photocopying of articles in lieu of loan of the original be done to a greater extent, and that standardized procedures in handling requests be instituted.

Costs and Cost Analysis↗
PubMed1993

Failure to obtain hybridomas between human macrophages and human tumoral U-937 cells is probably due to parental macrophages.

Despite more than 50 attempts and the use of various methods, it has been impossible to establish homologous hybridomas between human mature macrophages and 8-azaguanine-resistant U-937 clones prepared in the laboratory. To rule out the possibility that these clones were unsuitable for the selection of hybrids, a study of their properties was done. It was shown that U-937 wild type cells were able to produce HPRT, whereas 8-azaguanine (8-aza)-resistant clones did not. Curiously, exonic and intronic HPRT sequences were undetectable both in wild type and in 8-aza-resistant cell genomes, under conditions where they were detected in control cells. Chromosome analysis of the clone UM9, one of the most frequently used in fusion experiments, revealed many qualitative and quantitative differences with the U-937 wild type cells. 8-aza-resistant U-937 cells were capable of fusion with human macrophages and gave rise to heterokaryons and probably to synkaryons, which survived for weeks without dividing in hypoxanthine-aminopterin-thymidine medium. The results could be interpreted in terms of the existence of a transacting negative regulatory mechanism of the macrophage genome on the proliferative capacity of homospecific hybridomas.

Animals↗
PubMed2003

Men, masculinity, and the contexts of help seeking.

Research on men's help seeking yields strategies for enhancing men's use of mental and physical health resources. Analysis of the assumptions underlying existing theory and research also provides a context for evaluating the psychology of men and masculinity as an evolving area of social scientific inquiry. The authors identify several theoretical and methodological obstacles that limit understanding of the variable ways that men do or do not seek help from mental and physical health care professionals. A contextual framework is developed by exploring how the socialization and social construction of masculinities transact with social psychological processes common to a variety of potential help-seeking contexts. This approach begins to integrate the psychology of men and masculinity with theory and methodology from other disciplines and suggests innovative ways to facilitate adaptive help seeking.

Adult↗
PubMed2006

Perpetration of partner violence and HIV risk behaviour among young men in the rural Eastern Cape, South Africa.

OBJECTIVES: To examine associations between the perpetration of intimate partner violence and HIV risk behaviour among young men in rural South Africa. DESIGN: An analysis of baseline data from men enrolling in a randomized controlled trial of the behavioural intervention, Stepping Stones. METHODS: Structured interviews with 1275 sexually experienced men aged 15-26 years from 70 villages in the rural Eastern Cape. Participants were asked about the type, frequency, and timing of violence against female partners, as well as a range of questions about HIV risk behaviours. RESULTS: A total of 31.8% of men reported the perpetration of physical or sexual violence against female main partners. Perpetration was correlated with higher numbers of past year and lifetime sexual partners, more recent intercourse, and a greater likelihood of reporting casual sex partners, problematic substance use, sexual assault of non-partners, and transactional sex. Men who reported both physical and sexual violence against a partner, perpetration both before and within the past 12 months, or more than one episode of perpetration reported significantly higher levels of HIV risk behaviour than men who reported less severe or less frequent perpetration of violence. CONCLUSION: Young men who perpetrate partner violence engage in significantly higher levels of HIV risk behaviour than non-perpetrators, and more severe violence is associated with higher levels of risky behaviour. HIV prevention interventions must explicitly address the links between the perpetration of intimate partner violence and HIV risk behaviour among men, as well as the underlying gender and power dynamics that contribute to both.

Adolescent↗
PubMed1993

Functional analysis of human foamy virus accessory reading frames.

Foamy viruses belong to the retroviruses which possess a complex genome structure. The human foamy virus (HFV) isolate bears three open reading frames (the so-called bel genes) in the 3' region of the genome which have been reported to give rise to possibly six different proteins via alternative splicing (W. Muranyi and R. M. Flügel, J. Virol. 65:727-735, 1991). In order to analyze the requirements of these proteins for HFV replication in vitro, we constructed a set of single and combinatory bel gene mutants of an infectious molecular clone of HFV. The mutant which lacked the transacting activator, bel-1, was found to be replication incompetent. All other mutants replicated equally well and gave rise to comparable titers of infectious cell-free virus. When HFV proviruses were put under the control of a heterologous promoter (simian virus 40), none of the accessory gene products was found to be required for expression of structural (gag) proteins. There was no evidence for a posttranscriptional regulatory protein that is present in other complex retroviruses.

Base Sequence↗