[The cure of type 2 diabetes and patient education]. / Guérison du diabète de type 2 et éducation thérapeutique.

Type 2 diabetes is a potentially reversible disease. Patient education encompasses a deep investment of the health care providers, who with the aid of pedagogic tools, help the pa tient commit to this path. This facilitates the learning of uncommon knowledge and skills required. Whether or not it leads to a complete remission of the disease may not be the main purpose. The main goal lies in the patient's motivation to learn and change on a long term basis.

[Rehabilitation: a case for obese patients?]. / Readaptation: les patients obèses aussi?

In the word obesity, a clinical concept of chronic systemic disease pairs up with pejorative individual or social representations. Being obese is also facing situations of disability, organ failure, uncertainty of the fate and stigmatization. A care concept inspired by rehabilitation and therapeutic patient education could offer a new way and other purposes to the treatment of obesity. Restoring functions, learning how to adapt and change their environment, obese people may live better today, out of their isolation and develop partners in their projects of life and health. Rehabilitation of an obese patient is much more than weight loss!

[Understanding the life of the obese patient. A contribution to therapeutic patient education]. / Comprendre l'expérience de vie des personnes obèses: un apport pour l'éducation thérapeutique du patient.

This article presents an approach of obesity centered on patients' experience. How is obesity defined by these latter? Is it considered as a disease? Is it apprehended by them as an element to fight or as a potentially meaningful event? Has the sick person the feeling to suffer from obesity or to have resources to face it? At the crossroads of three human sciences (sociology, anthropology and education), this approach aims to enrich and increase the efficiency of therapeutic patient education for obese patients. Extended experience narration extracts are presented in this article, obtained from research interviews. They show the importance of taking into account the "subjective experience" of the disease when accompanying persons affected by obesity.

Therapeutic education of diabetic patients.

Therapeutic patient education is a patient-centred approach, focussed on patients' needs, resources, values and strategies. It allows patients to improve their knowledge and skills not only concerning their illness but also their treatment. It brings a better quality of life, a greater therapeutic compliance and a reduction in complications. The most difficult part of therapeutic patient education occurs when patients must change their behaviour. Motivational interviewing and cognitive-behavioural approaches contribute greatly here and allow both the preparation and support of patients during progressive 'step by step' change. The work on resistance to change is fundamental, and ambivalence when faced with the choice of a new way of life must be measured, discussed and negotiated. Patients become partners and we become 'coaches'. The negotiation of objectives must allow patients to choose their own strategies, which normally should cost them the least possible, psychologically, and bring them the maximum benefit. The efficiency of therapeutic patient education no longer needs to be proved: 80% less amputations over 10 years in diabetic patients; 50% maintenance of weight loss over 5 years, etc. In conclusion, therapeutic education is part of a humanistic medical approach centred on patients; it allows them to be active participants in their own treatment with the aim of improving their quality of life and therapeutic compliance, as well as reducing potential complications. Thus, health care professionals teach, inform, train, negotiate with, motivate and accompany patients in the long-term follow-up of their illness.

[Therapeutic education of the diabetic patient]. / L'enseignement thérapeutique: application au patient diabétique.

Therapeutic education is a patient centred approach focused on patients' needs, values and strategies. It allows not only to increase patients' knowledge and skills on the disease, but also on their treatments. It brings a better quality of life, an increased therapeutic compliance, and decreases complications. The most difficult part of therapeutic education occurs when patients must change their behaviour. Motivational interviewing techniques are of great support and allow to prepare and support patients in "step by step" progressive changes. It is essential to work on resistance to change. The ambivalence in the choice of a new lifestyle must be measured, discussed and negotiate. Patients become partners and health care providers become coaches. To negotiate objectives must allow patients to choose their own strategies which should cost them minimum psychological efforts and bring them maximum benefits. The efficacy of therapeutic education has not to be proved any more: 80% less of amputations at 10 years in diabetic patients, 50% of stable body weight after weight loss at 5 years, etc. In conclusion, therapeutic education is part of a humanist medicine centred on patients which allow them to take care of their own treatment, in order to improve their quality of life, therapeutic compliance and potential complications. The health care providers teach, train, negotiate, motivate and accompany their patients in the long-term follow-up of their diseases.

Histone deacetylase 1 can repress transcription by binding to Sp1.

The members of the Sp1 transcription factor family can act as both negative and positive regulators of gene expression. Here we show that Sp1 can be a target for histone deacetylase 1 (HDAC1)-mediated transcriptional repression. The histone deacetylase inhibitor trichostatin A activates the chromosomally integrated murine thymidine kinase promoter in an Sp1-dependent manner. Coimmunoprecipitation experiments with Swiss 3T3 fibroblasts and 293 cells demonstrate that Sp1 and HDAC1 can be part of the same complex. The interaction between Sp1 and HDAC1 is direct and requires the carboxy-terminal domain of Sp1. Previously we have shown that the C terminus of Sp1 is necessary for the interaction with the transcription factor E2F1 (J. Karlseder, H. Rotheneder, and E. Wintersberger, Mol. Cell. Biol. 16:1659-1667, 1996). Coexpression of E2F1 interferes with HDAC1 binding to Sp1 and abolishes Sp1-mediated transcriptional repression. Our results indicate that one component of Sp1-dependent gene regulation involves competition between the transcriptional repressor HDAC1 and the transactivating factor E2F1.

Histone H4 acetylation during interleukin-2 stimulation of mouse T cells.

Proliferation and cell cycle progression of eukaryotic cells are closely linked to changes in chromatin structure and gene expression. By reversible histone acetylation the cell is able to modulate chromatin condensation and accessibility of specific regions within the chromatin. Here, we examined histone H4 acetylation patterns during growth induction of the murine interleukin-2 dependent T cell line B6.1. In order to detect acetylation on each of the four potential target residues we produced a set of antibodies recognizing specifically acetylated lysine 5, 8, 12 and 16 in the N-terminal tail of histone H4. Acetylation was generally low in resting T cells, but increased after stimulation with a specific kinetics for each lysine. Lysine 16 was acetylated during the G1 phase and deacetylated during S phase. H4 acetylation on lysine 5, 8 and 12, in contrast, was induced before cells started to replicate, and persisted until cells entered mitosis. Treatment of resting B6.1 cells with the specific deacetylase inhibitor trichostatin A (TSA) led to H4 hyperacetylation at all four lysine residues indicating that the histone modification can occur in the absence of replication. After release from TSA treatment normal H4 acetylation levels were reestablished by extremely rapid deacetylation of lysines 5, 8, 12 and 16. The deacetylation step was 60-100 times faster than TSA induced acetylation and equally efficient in resting and exponentially growing T cells. Our results indicate the presence of cell cycle regulated lysine specific acetylating and deacetylating activities in mouse T cells.

The thyroid hormone receptor functions as a ligand-operated developmental switch between proliferation and differentiation of erythroid progenitors.

The avian erythroblastosis virus (AEV) oncoprotein v-ErbA represents a mutated, oncogenic thyroid hormone receptor alpha (c-ErbA/ TRalpha). v-ErbA cooperates with the stem cell factor-activated, endogenous receptor tyrosine kinase c-Kit to induce self-renewal and to arrest differentiation of primary avian erythroblasts, the AEV transformation target cells. In this cooperation, v-ErbA substitutes for endogenous steroid hormone receptor function required for sustained proliferation of non-transformed erythroid progenitors. In this paper, we propose a novel concept of how v-ErbA transforms erythroblasts. Using culture media strictly depleted from thyroid hormone (T3) and retinoids, the ligands for c-ErbA/TRalpha and its co-receptor RXR, we show that overexpressed, unliganded c-ErbA/ TRalpha closely resembles v-ErbA in its activity on primary erythroblasts. In cooperation with ligand-activated c-Kit, c-ErbA/ TRalpha causes steroid-independent, long-term proliferation and tightly blocks differentiation. Activation of c-ErbA/ TRalpha by physiological T3 levels causes the loss of self-renewal capacity and induces synchronous, terminal differentiation under otherwise identical conditions. This T3-induced switch in erythroid progenitor development is correlated with a decrease of c-ErbA-associated histone deacetylase activity. Our results suggest that the crucial role of the mutations activating v-erbA as an oncogene is to 'freeze' c-ErbA/ TRalpha in its non-liganded, repressive conformation and to facilitate its overexpression.

Identification of mouse histone deacetylase 1 as a growth factor-inducible gene.

Reversible acetylation of core histones plays an important role in transcriptional regulation, cell cycle progression, and developmental events. The acetylation state of histones is controlled by the activities of acetylating and deacetylating enzymes. By using differential mRNA display, we have identified a mouse histone deacetylase gene, HD1, as an interleukin-2-inducible gene in murine T cells. Sequence alignments revealed that murine HD1 is highly homologous to the yeast RPD3 pleiotropic transcriptional regulator. Indirect immunofluorescence microscopy proved that mouse HD1 is a nuclear protein. When expressed in yeast, murine HD1 was also detected in the nucleus, although it failed to complement the rpd3delta deletion phenotype. HD1 mRNA expression was low in G0 mouse cells but increased when the cells crossed the G1/S boundary after growth stimulation. Immunoprecipitation experiments and functional in vitro assays showed that HD1 protein is associated with histone deacetylase activity. Both HD1 protein levels and total histone deacetylase activity increased upon interleukin-2 stimulation of resting B6.1 cells. When coexpressed with a luciferase reporter construct, HD1 acted as a negative regulator of the Rous sarcoma virus enhancer/promoter. HD1 overexpression in stably transfected Swiss 3T3 cells caused a severe delay during the G2/M phases of the cell cycle. Our results indicate that balanced histone acetylation/deacetylation is crucial for normal cell cycle progression of mammalian cells.