The need for a telemedicine strategy for Botswana? A scoping review and situational assessment.

BACKGROUND: Health, healthcare, and healthcare system problems within the developing world are well recognised. eHealth, the use of Information and Communications Technologies (ICT) for health, is frequently suggested as one means by which to ameliorate such problems. However, to identify and implement the most appropriate ehealth solutions requires development of a thoughtful and broadly evidence-informed strategy. Most published strategies focus on health informatics solutions, neglecting the potential for other aspects of ehealth (telehealth, telemedicine, elearning, and ecommerce). This study examined the setting in Botswana to determine the need for a telemedicine-specific strategy. METHODS: A situational assessment of ehealth activities in Botswana was performed through a scoping review of the scientific and grey literature using specified search terms to July 2018; an interview with an official from the major mhealth stakeholder; and benchtop review of policies and other relevant Government documents including the country's current draft eHealth Strategy. RESULTS: Thirty-nine papers were reviewed. Various ehealth technologies have been applied within Botswana. These include Skype for educational activities, instant messaging (WhatsApp for telepathology; SMS for transmission of laboratory test results, patient appointment reminders, and invoicing and bill payment), and robotics for dermatopathology. In addition health informatics technologies have been used for surveillance, monitoring, and access to information by healthcare workers. The number of distinct health information systems has been reduced from 37 to 12, and 9 discrete EMRs remain active within the public health institutions. Many infrastructural issues were identified. A critical assessment of the current draft ehealth strategy document for Botswana showed limitations. Many telemedicine services have been introduced over the years (addressing cervical cancer screening, teledermatology, teleradiology, oral medicine and eye screening), but only one project was confirmed to be active and being scaled up with the intervention of the Government. CONCLUSIONS: Botswana's draft 'ehealth' strategy will not, in and of itself, nurture innovative growth in the application of telemedicine initiatives, which currently are fragmented and stalled. This lack of focus is preventing telemedicine's recognised potential from being leveraged. A specific Telemedicine Strategy, aligned with and supportive of the pre-existing ehealth strategy, would provide the necessary focus, stimulus, and guidance.

The development of ethical guidelines for telemedicine in South Africa

Telemedicine has the potential to assist in the provision of healthcare in South Africa (SA). This means of healthcare service provision involves patients, doctors and machines working together, with few constraints imposed by geography, or national or institutional boundaries. Although the practice is largely beneficial, certain legal and ethical challenges arise from the use of electronic healthcare services. Certain ethical challenges are identified as: the changing nature of the traditional doctor-patient relationship; standards of care;quality of care; privacy; confidentiality; data protection; accountability; liability; consent; record-keeping; data storage; and authentication.While various legal, regulatory and governance measures offer potential solutions and remedies for protection, ethical direction may be achieved through statutory bodies set up to promote and foster ethical compliance with normative healthcare standards. Recently, the Health Professions Council of SA (HPCSA) made an attempt to address the ethical issues by publishing a set of telemedicine guidelines.Despite this, issues around the practice of telemedicine remain unresolved. This article seeks to inform the development of a new ethical framework by addressing three distinct and relevant ethical issues: the fiduciary nature of healthcare and the changing nature of the doctor-patient relationship; privacy, confidentiality and the sensitivity of health data; and informed consent. It does so by proposing a broader and more nuanced solution to these ethical obstacles by identifying conceptual and operational difficulties within the existing HPCSA telemedicine guidelines, and advancing suggestions for reform. This speaks to a more highly integrated perspective that is culturally and contextually aware, and which affirms the need to strike a balance between individual rights protection and transformative, ethical, healthcare innovation

Quantitative measures for redox signaling.

Redox signaling is now recognized as an important regulatory mechanism for a number of cellular processes including the antioxidant response, phosphokinase signal transduction and redox metabolism. While there has been considerable progress in identifying the cellular machinery involved in redox signaling, quantitative measures of redox signals have been lacking, limiting efforts aimed at understanding and comparing redox signaling under normoxic and pathogenic conditions. Here we have outlined some of the accepted principles for redox signaling, including the description of hydrogen peroxide as a signaling molecule and the role of kinetics in conferring specificity to these signaling events. Based on these principles, we then develop a working definition for redox signaling and review a number of quantitative methods that have been employed to describe signaling in other systems. Using computational modeling and published data, we show how time- and concentration- dependent analyses, in particular, could be used to quantitatively describe redox signaling and therefore provide important insights into the functional organization of redox networks. Finally, we consider some of the key challenges with implementing these methods.

Health needs and eHealth readiness assessment of health care organizations in Kabul and Bamyan, Afghanistan.

This study assessed the need and readiness of health care institutions in Kabul and Bamyan, Afghanistan for successful implementation of information and communication technology in health care (eHealth). A mixed methods design was adopted at 2 institutions in the Aga Khan Development Network in Afghanistan: the French Medical Institute for Children in Kabul and Bamyan Provincial Hospital, Bamyan. Information for the needs assessment was obtained from interviews and focus groups and eHealth readiness was assessed using a validated survey tool. The needs of institutions in the Aga Khan Development Network in Afghanistan were categorized as follows: provision of care needs; learning needs; and information management needs. eHealth readiness on average was lower in Bamyan compared with Kabul in all areas of the readiness assessment. Other institutions in Afghanistan may benefit from adopting the model of needs and readiness assessment used for Aga Khan Development Network institutions.

Health needs and eHealth readiness assessment of health care organizations in Kabul and Bamyan, Afghanistan

This study assessed the need and readiness of health care institutions in Kabul and Bamyan, Afghanistan for successful implementation of information and communication technology in health care [eHealth]. A mixed methods design was adopted at 2 institutions in the Aga Khan Development Network in Afghanistan: the French Medical Institute for Children in Kabul and Bamyan Provincial Hospital, Bamyan. Information for the needs assessment was obtained from interviews and focus groups and eHealth readiness was assessed using a validated survey tool. The needs of institutions in the Aga Khan Development Network in Afghanistan were categorized as follows: provision of care needs; learning needs; and information management needs. eHealth readiness on average was lower in Bamyan compared with Kabul in all areas of the readiness assessment. Other institutions in Afghanistan may benefit from adopting the model of needs and readiness assessment used for Aga Khan Development Network institutions

Faecal sludge in Accra, Ghana: problems of urban provision.

Urban on-site sanitation services present challenges for emptying, transporting, disposing and treating faecal waste. Transfer stations can be used by household-level emptiers to safely dispose of faecal sludge, but they rarely exist. Accra's use of transfer stations has provided an opportunity to research their functioning, as part of broader faecal sludge management arrangements. The paper discusses the benefits offered by use of transfer stations, as well as reasons currently limiting their operation. While costs associated with operating and emptying these stations are passed to householders, an illegal sector thrives offering lower cost emptying services, typically with disposal of faecal sludge directly into the environment. At present, bucket latrines offer sanitation services to low-income households unable to afford higher service levels, such as septic tanks. The local government aims to phase-out all bucket latrines by 2010, but affordable alternatives have not been found. Where limited access to land inhibits investment in permanent facilities, families may abandon household sanitation altogether. The paper concludes that correct use of transfer stations can provide improvements for existing faecal sludge management and reduce indiscriminate dumping. They must be made available to all workers, through effective public-private arrangements for ownership and operation.

Policy implications associated with the socioeconomic and health system impact of telehealth: a case study from Canada.

This research was undertaken to inform future telehealth policy directions regarding the socioeconomic impact of telehealth. Fifty-seven sources were identified and analyzed through a comprehensive literature search of electronic databases, the Internet, journals, conference proceedings, as well as personal communication with consultants in the field. The review revealed a focus on certain socioeconomic indicators such as cost, access, and satisfaction. It also identified areas of opportunity for further research and policy analysis and development (e.g., social isolation, life stress, poverty), along with various barriers and challenges to the advancement of telehealth. These included confidentiality, reimbursement, and legal and ethical considerations. To become fully integrated into the health care system, telehealth must be viewed as more than an add-on service. This paper offers 19 general and 20 subject-specific telehealth recommendations, as well as seven policy strategies.

The socio-economic impact of telehealth: a systematic review.

We reviewed the socio-economic impact of telehealth, focusing on nine main areas: paediatrics, geriatrics, First Nations (i.e. indigenous peoples), home care, mental health, radiology, renal dialysis, rural/remote health services and rehabilitation. A systematic search led to the identification of 4646 citations or abstracts; from these, 306 sources were analysed. A central finding was that telehealth studies to date have not used socio-economic indicators consistently. However, specific telehealth applications have been shown to offer significant socio-economic benefit, to patients and families, health-care providers and the health-care system. The main benefits identified were: increased access to health services, cost-effectiveness, enhanced educational opportunities, improved health outcomes, better quality of care, better quality of life and enhanced social support. Although the review found a number of areas of socio-economic benefit, there is the continuing problem of limited generalizability.

Stable overexpression of specific segments of the P2P-R protein in human MCF-7 cells promotes camptothecin-induced apoptosis.

The stable overexpression of near full-length P2P-R protein in human Saos 2 cells restricts cell cycle progression by inducing mitotic arrest at prometaphase and mitotic apoptosis (Gao and Scott, 2002). Those effects of P2P-R were observed in Saos-2 cells that lack p53 and employ a caspase-3-dependent apoptotic signaling pathway. The current studies were performed to evaluate if overexpression of specific segments of the P2P-R protein promote apoptosis in human MCF-7 cells that contain p53 and employ a different apoptotic signaling pathway. Since segments of P2P-R were found not to induce apoptosis independently, the ability of three different P2P-R segments to promote camptothecin-induced apoptosis was evaluated following their stable transfection and expression in MCF-7 cells. Relative to full-length P2P-R (1-1560 aa), the three P2P-R segments used in these studies included: P2P-R-2 (761-1560 aa), P2P-R-3 (1156-1560 aa), and P2P-R-4 (1314-1560 aa). The results document that overexpression of P2P-R-2 and P2P-R-3 promotes camptothecin-induced apoptosis by three to fivefold when assayed by flow cytometric analysis of apoptotic sub 2n cell populations or by TUNEL assays. In contrast, P2P-R-4 had no effect on apoptosis. These results suggest that the ability of P2P-R to promote camptothecin-induced apoptosis in MCF-7 cells involves a specific region (1156-1314 aa) that exists within P2P-R. The data presented also show that the p53 binding domain of P2P-R overlaps with the apoptosis-associated region and previous studies documented that this region of P2P-R also binds single-strand nucleotides (Witte and Scott, 1997). Therefore, P2P-R-promoted apoptosis induced by camptothecin may be influenced by such interactions.

Regulation and expression of progesterone receptor mRNA isoforms A and B in the male and female rat hypothalamus and pituitary following oestrogen treatment.

Progesterone receptors play a central role in neuroendocrine and behavioural regulation. To gain insight into the sex- and tissue-specific regulation of progesterone receptors, protein binding on a progesterone receptor-oestrogen response element and mRNA levels for progesterone receptor (PR)-A and PR-B were compared between female and male rats following oestradiol benzoate replacement treatment in hypothalamic and pituitary tissue. Both male and female pituitary protein extracts demonstrated an increase in nuclear protein binding activity to a progesterone receptor-oestrogen response element following oestradiol benzoate treatment. However, there was a greater difference in total binding activity seen in the female pituitary extracts compared to male pituitary protein extracts. In both cases, reflecting the binding data, oestradiol benzoate pretreatment led to an increase in pituitary PR-B messenger RNA, although this increase was significantly larger in females than in males. Oestradiol benzoate treatment also led to a significant increase in specific binding of hypothalamic nuclear proteins to the progesterone receptor oestrogen response element from both females and male hypothalamic extracts. In addition, PR-B messenger RNA was induced by oestradiol benzoate treatment in the female rat hypothalamus, under circumstances where no PR-A could be detected. The male also demonstrated an increase in PR-B messenger RNA following oestradiol benzoate treatment, with undetectable levels of PR-A, although to a lesser degree than that seen in the female. The predominance of PR-B over PR-A messenger RNA in rat hypothalamus and pituitary, and the quantitative differences between female and male rats, could both contribute to the greater responsiveness of female rats to progesterone with respect to control over luteinizing hormone release from the pituitary, and lordosis behaviour regulated by hypothalamic neurones.

P2P-R deficiency modifies nocodazole-induced mitotic arrest and UV-induced apoptosis.

BACKGROUND: Cell cycle progression from G1 through S to mitosis can be influenced by microtubule-dependent mechanisms that involve AP1 factors and c-Jun N-terminal kinase (JNK) activity. UV irradiation-induced apoptosis also involves AP1 factors and JNK activity. The current studies evaluated the outcome of P2P-R deficiency on these mechanisms because P2P-R expression is repressed in association with a decrease in AP1 inducibility and cell cycle progression during differentiation, and P2P-R overexpression promotes apoptosis. MATERIALS AND METHODS: The ability of the microtubule disruption drug nocodazole to induce mitotic arrest and the ability of UV irradiation to induce apoptosis was evaluated in native versus cells made P2P-R deficient by P2P-R antisense treatment. RESULTS: P2P-R deficiency restricts cell cycle progression from G1 through S to mitosis in a microtubule-dependent manner and P2P-R deficiency represses UV irradiation-induced apoptosis. CONCLUSION: P2P-R may influence AP1 and/or JNK signaling pathways.

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.

Transformation blocks differentiation-induced inhibition of serum response factor interactions with serum response elements.

The differentiation of nontransformed 3T3T mesenchymal stem cells is a multistep process that is associated with the progressive repression of mitogenic responsiveness to serum growth factors that ultimately results in expression of the terminally differentiated adipocyte phenotype. The repression of serum-induced mitogenesis by differentiation correlates with repression of the serum-inducible transcription of junB and c-fos. In contrast, the differentiation of neoplastically transformed cells does not repress mitogenic responsiveness or junB or c-fos inducibility. Because the junB and c-fos promoters both contain serum response elements (SREs), the current studies tested the possibility that differentiation might repress the ability of serum response factor (SRF) to bind to the SRE in normal cells but not in transformed cells. We now report that differentiation represses SRE serum inducibility using nontransformed cells transiently transfected with pjunB SRE thymidine kinase/chloroamphenicol acetyltransferase (SREtk/CAT) or pc-fos SREtk/CAT containing an intact SRF-binding domain. Adipocyte differentiation of nontransformed cells also markedly represses the ability of SRF to bind to the junB SRE, the c-fos SRE, and other SREs, as determined by mobility shift and gel supershift assays, without affecting the DNA binding characteristics of the nuclear protein SP-1. By comparison, the ability of SRF to bind SRE is not repressed by the differentiation of SV40 large T antigen-transformed 3T3T cells. The results further establish that adipocyte differentiation blocks the nuclear localization of SRF, thus preventing its interaction with SREs in nontransformed cells but not in transformed cells.

The value of an evaluation framework for telehealth initiatives.

Healthcare managers and policy makers will, in the immediate and near future, make major decisions about the allocation of scarce healthcare resources for telehealth 'solutions'. In our haste to capitalize on what technology can do we may be obscuring discussion and research about what technology should do. For example, currently much attention is being paid to standardization for technological aspects of telehealth. In contrast few efforts have been made to seek standardization in regards to a broad evaluation framework for telehealth. A body of opinion believes that missing in our rush into the on-line world is a systematic approach to research into the human, social, cultural, economic, and political factors associated with healthcare. As a result we lack the tools and experience necessary to assess the true value and implications of telehealth 'solutions'. Developing general guidelines for an evaluation framework, from needs assessment through integrated research to post-study assessment, would greatly enhance the quality of decision making by healthcare managers and policy makers. We propose a model--the Telehealth Integrated Research Model (TIRM)--as the first step in encouraging discussion and development of an internationally accepted standardized telehealth evaluation framework.

Interactions of estrogen- and thyroid hormone receptors on a progesterone receptor estrogen response element (ERE) sequence: a comparison with the vitellogenin A2 consensus ERE.

The identification of hormone response elements in the promoter regions of hormonally regulated genes has revealed a striking similarity between the half-site of the estrogen-response element (ERE) and a consensus sequence constituting the thyroid hormone-response element. Because of the potential for thyroid hormone (T3) to affect estrogen (E)- and progesterone-dependent female reproductive behavior via EREs, we have begun to investigate the activity of an ERE identified in the progesterone receptor (PR) proximal promoter and its interactions with the estrogen receptor (ER) and thyroid hormone receptors (TR). In addition, we have compared ER and TR interactions on the PR ERE construct with that of the vitellogenin A2 (vit A2) consensus ERE. Electrophoretic mobility shift assays demonstrated that TR binds to the PR ERE as well as to the consensus ERE sequence in vitro. Further, these two EREs were differentially regulated by T3 in the presence of TR. T3 in the presence of TR alpha increased transcription from a PR ERE construct approximately 5-fold and had no inhibitory effect on E induction. Similarly, T3 also activated a beta-galactosidase reporter construct containing PR promoter sequences spanning -1400 to +700. In addition, the TR isoforms beta1 and beta2 also stimulated transcription from the PR ERE construct by 5- to 6-fold. A TR alpha mutant lacking the ability to bind AGGTCA sequences in vitro failed to activate transcription from the PR ERE construct, demonstrating dependence on DNA binding. In contrast to its actions on the PR ERE construct, TR alpha did not activate transcription from the vit A2 consensus ERE but rather attenuated E-mediated transcriptional activation. Attenuation from the vit A2 consensus ERE is not necessarily dependent on DNA binding as the TR alpha DNA binding mutant was still able to inhibit E-dependent transactivation. In contrast to TR alpha, the isoforms TRbeta1 and TRbeta2 failed to inhibit E-induced activation from the vit A2 consensus ERE. These results demonstrate that the PR ERE construct differs from the vit A2 consensus ERE in its ability to respond to TRs and that divergent pathways exist for activation and inhibition by TR. Since ERs, PRs, and TRs are all present in hypothalamic neurons, these findings may be significant for endocrine integration, which is important for reproductive behavior.

Induction of AP-1 activity associated with c-Jun and JunB is required for mitogenesis induced by insulin and vanadate in SV40-transformed 3T3T cells.

Insulin and vanadate function as complete mitogens for SV40-transformed murine 3T3T (CSV3-1) cells but not for nontransformed 3T3T cells. Mitogenesis induced by insulin and vanadate in CSV3-1 cells is associated with the induction of the expression of protooncogenes c-jun and junB, two major AP-1 transcription factor components. We now report that both insulin and vanadate induce a significant increase in AP-1 DNA binding activity in CSV3-1 cells but not in 3T3T cells. Gel supershift assays and Western blot analysis using specific antibodies demonstrate that the increased AP-1 binding activity induced by insulin and vanadate in CSV3-1 cells is primarily contributed by an increase in the expression of c-Jun and JunB protein levels. Furthermore, treatment of CSV3-1 cells with antisense oligodeoxyribonucleotides to c-jun or to junB blocks insulin- and vanadate-induced mitogenesis whereas antisense junD oligomers have no inhibitory effects. These results therefore demonstrate that the induction of AP-1 binding activity associated with c-Jun and JunB is required for insulin- and vandate-induced mitogenesis in SV40-transformed murine 3T3T cells. Additional data presented in this paper show that JunD/AP-1 binding activity, which is thought to play a negative role in regulating cell proliferation, is also slightly induced following insulin and vanadate stimulation in CSV3-1 cells. Nevertheless, the ratio of proliferation promoting c-Jun/AP-1 and JunB/AP-1 binding activities to proliferation inhibiting JunD/AP-1 binding activity is significantly increased following insulin and vanadate stimulation. These results therefore support the concept that modulation of the balance of positive Jun/AP-1 and negative Jun/AP-1 activities is important in regulating cell proliferation.

The proliferation potential protein-related (P2P-R) gene with domains encoding heterogeneous nuclear ribonucleoprotein association and Rb1 binding shows repressed expression during terminal differentiation.

Terminal differentiation is associated with repression in the expression of the proliferation potential proteins (P2P) subset of heterogeneous nuclear ribonucleoprotein (hnRNP) proteins. We report here the cloning and characterization of a 5173-bp P2P-related (P2P-R) cDNA that contains a 4214-bp open reading frame. Probes to this cDNA detect a single 8-kb mRNA in multiple murine tissues and in proliferating 3T3T cells, but not in terminally differentiated 3T3T adipocytes. Evidence that this cDNA can encode peptides with domains for hnRNP association was established by showing that such peptides are recognized by two monoclonal antibodies known to detect core hnRNP proteins, and by showing that the C130 monoclonal antibody, produced against a cDNA-derived fusion protein, also selectively detects native P2P hnRNP proteins. In addition, P2P-R cDNA-derived fusion proteins bind single-stranded nucleic acids, and a P2P-R cDNA-derived antisense oligonucleotide selectively represses P2P expression. Because terminal differentiation is associated with modulation in Rb1 function, we assayed if products of this cDNA might interact with Rb1. Evidence that the P2P-R cDNA encodes a protein domain that binds Rb1 was established using a glutathione S-transferase fusion protein to selectively precipitate Rb1 from cellular extracts. Data also show that this binding is reduced by competition with the adenovirus E1a protein, indicating that binding occurs through the "pocket" domain of Rb1. These results establish that the P2P-R cDNA encodes protein domains involved in both hnRNP association and Rb1 binding and complement recent reports that localize Rb1 to sites of RNA processing in the nucleus.

Serum deprivation induces SV40 early promoter activity.

Proliferation and the expression of proliferation-associated genes are modulated by changing the serum concentration in the media of cultured cells. To determine if activity of the SV40 early promoter is modulated by serum, we examined the expression of SV40 early promoter driven marker genes in murine BALB/c 3T3T cells following serum deprivation or serum stimulation. SV40-promoter-regulated beta-galactosidase and chloramphenicol acetyl transferase genes were studied following either transient or stable transfection. The results show that serum deprivation of growing cells induces SV40 promoter activity while serum stimulation of quiescent G0 cells suppresses it. Kinetic analyses show a significant induction of the SV40 promoter activity during the first 2 days of serum deprivation which is maintained at a high level for 15 days. The induction of reporter gene expression by serum deprivation was selective for the SV40 early promoter because such an effect was not observed using the Rous sarcoma viral promoter. Nuclear run-off assays further show that the transcription controlled by the SV40 early promoter is approximately twofold greater in cells rendered quiescent by serum deprivation for 72 h than in growing cells cultured in medium containing serum. These results suggest that one reason SV40 T transformed cells commonly fail to undergo quiescence following serum deprivation is that the SV40 promoter is induced.

Differentiation, differentiation/gene therapy and cancer.

"Differentiation, Differentiation/Gene Therapy and Cancer" is intended to suggest that an understanding of the cell and molecular biology of cell differentiation should advance the development of new cancer therapies. This article, therefore, reviews four general topics and their relationship to each other: (1) the multistep process of cell differentiation in nontransformed and transformed cells, (2) the use of drugs that induce differentiation in vitro as potential clinical differentiation therapy agents for cancer, (3) the evolving emphasis on gene therapy as a new cancer therapy modality, and (4) the concept of differentiation/gene therapy.

JunD phosphorylation, and expression of AP-1 DNA binding activity modulated by serum growth factors in quiescent murine 3T3T cells.

JunD has been implicated as a negative regulator of cell proliferation. If and how JunD is regulated by growth factors however has not been well investigated. We now report that in quiescent murine 3T3T cells, JunD is present in a hypophosphorylated form, but that when quiescent cells are stimulated to proliferate with serum, JunD undergoes a transient increase in its phosphorylation that occurs within 10 min and persists for up to 4 h. The increase in JunD phosphorylation correlates with the induction of cell proliferation since only those growth factors that promote cell proliferation can induce JunD phosphorylation. Treatment of quiescent 3T3T cells with serum also induces significant decreases in JunD/AP-1 DNA binding activity within 2 h and in JunD expression after 8-48h. However, both hypophosphorylated and hyperphosphorylated forms of JunD can bind AP-1 DNA. These results suggest that serum growth factors can modulate JunD characteristics in a variety of apparently independent ways to overcome its negative regulatory effect in controlling cell proliferation. These include induction of a transient increase in JunD phosphorylation, repression of JunD AP-1 DNA binding activity and downregulation of JunD expression.