Common genetic variation near MC4R is associated with eating behaviour patterns in European populations.

Both rs17782313 (near MC4R) and rs1421085 (FTO) polymorphisms have been consistently associated with increased risk of obesity and with body mass index (BMI) variation. An effect of both polymorphisms on satiety has recently been suggested. We genotyped rs17782313 and rs1421085 in 5764 relatives from 1109 French pedigrees with familial obesity, 1274 Swiss class III obese adults as well as in 4877 French adults and 5612 Finnish teenagers from two randomly selected population cohorts. In all subjects, eating behaviour traits were documented through questionnaires. We first assessed the association of both single nucleotide polymorphisms with BMI and then studied eating behaviour. Under an additive model, the rs17782313-C MC4R allele showed a trend towards higher percentages of snacking in both French obese children (P=0.01) and Swiss obese adults (P=0.04) as well as in adolescents from the Finnish general population (P=0.04). In French adults with familial obesity, this allele tended to be also associated with a higher Stunkard hunger score (P=0.02) and in obese children with a higher prevalence of eating large amounts of food (P=0.04). However, no consistent association of the FTO rs1421085-C allele and available eating behaviour trait was found in our studied populations. The rs17782313-C allele nearby MC4R may modulate eating behaviour-related phenotypes in European obese and randomly selected populations, in both children and adults, supporting a regulatory role of this genetic variant on eating behaviour, as previously shown for MC4R non-synonymous loss-of-function mutations. The potential effect of the obesity-associated FTO gene on eating behaviour deserves additional investigation.

A primary cutaneous non-T, non-B CD4+, CD56+ lymphoma.

BACKGROUND: Cutaneous lymphomas are heterogeneous clonal lymphoproliferative disorders originating from B or T lymphocytes. OBSERVATION: We describe a patient with a unique primary cutaneous lymphoma characterized by a bruise-like aspect of the skin lesions, a CD4+, CD43+, CD56+, CD2-, CD3-, CD8-, T-cell receptor-negative phenotype of the medium-sized to large lymphoid tumor cells and an undetermined genotype (T-cell receptor beta and immunoglobulin heavy chain in germline configuration, no clonal T-cell receptor gamma population as detected after analysis with polymerase chain reaction combined with denaturing gradient gel electrophoresis) and fast relapse after radiotherapy. CONCLUSIONS: This non-B, non-T cutaneous lymphoma cannot be classified by any current lymphoma classification. It seems to represent a new disease entity with peculiar clinical, histologic, and molecular features.

[Surgical procedures for severely obese patients: impact and long-term results]. / Chirurgische Verfahren bei krankhafter Adipositas. Stellenwert und Langzeitergebnisse.

Obesity is a multifactorial, genetically-determined, neuroendocrine, and chronic condition. Conservative treatment of patients with class II and III obesity (BMI >35 kg/m(2)) has only modest long-term success. Surgical procedures have been used since 1954, and the methods used are continually being updated and improved. With experienced surgeons, patients can achieve a weight reduction from around 50% with purely restrictive procedures, increasing to 75% with combined restrictive-malabsorptive methods. All weight-loss methods offer a considerable improvement or elimination of obesity-related co-morbidities and substantially improvement of quality of life. Well-documented, long-term studies reveal a perioperative mortality of 0.2-1.0%, dependent on the surgeon's experience, and a maximum perioperative morbidity of 20%. Bariatric surgery is accepted as evidence based, safe and effective treatment of obesity.

Interleukin-15 is an autocrine/paracrine viability factor for cutaneous T-cell lymphoma cells.

In this study we investigated the role of interleukin-15 (IL-15) in the immunobiology of cutaneous T-cell lymphoma (CTCL) cells. Using cell culture techniques, reverse transcriptase-polymerase chain reaction (RT-PCR), and immunhistochemistry we found that IL-15, like IL-7, is a growth factor for the Sézary cell line SeAx and that both cytokines prolonged the survival of malignant T cells directly isolated from Sézary syndrome (SS) patients. Both IL-15 and IL-7 were more potent than IL-2. IL-4 and IL-9, whose receptors share the same gamma chain with the receptors of IL-2, IL-7, and IL-15, did not sustain the growth of CTCL cells, indicating that signaling through the common gamma chain (gammac) is not sufficient for continuous growth. IL-13 and tumor necrosis factor-alpha (TNF-alpha) had no effect. IL-7 and IL-15 also supported the growth of SeAx cells in the presence of the apoptosis inducing agents dexamethasone and retinoic acid. The analysis of patient Sézary cells and three CTCL cell lines by RT-PCR showed that all these cells expressed IL-15 mRNA, but only a few (25%) produced IL-7 mRNA. Immunohistological analyses of skin biopsy samples of SS and Mycosis fungoides patients showed immunoreactivity for IL-15 in basal cell layer keratinocytes and in the infiltrating lymphocytes. We conclude that IL-15 is a growth or viability factor for CTCL-derived cell lines or shortly cultivated Sézary cells. The findings that IL-15 mRNA can be detected in Sézary syndrome peripheral blood mononuclear cells and that the IL-15 protein is detected in skin sections from CTCL patients suggest that IL-15 plays an important role in the biology of CTCL.

T-cell receptor beta variable region (V beta) usage in cutaneous T-cell lymphomas (CTCL) in comparison to normal and eczematous skin.

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of lymphoproliferative disorders. We investigated the variable region (V beta) of the T-cell receptor (TCR) repertoire in CTCL and compared it to the V beta repertoire in normal and eczematous skin. We used a panel of 21 anti-V beta antibodies and investigated 84 biopsies of 71 CTCL patients (4 parapsoriasis en grandes plaques (PA), 1 lymphomatoid papulosis, 29 mycosis fungoides (MF), 13 Sezary syndrome (SS), 1 CD8+ CTCL, 11 pleomorphic CTCL (PLEO), 12 CTCL nor classified). Six biopsies of normal skin and 6 of eczematous skin lesions served as controls. We determined the frequency of the V beta in normal and inflamed skin and compared it to the percentage of the respective V beta in the malignant clone of the CTCL patients. The percentage of the V beta positive CD4+ cells in relation to the total number of T cells in normal skin and inflamed skin differed from the distribution of the V beta families in the peripheral blood mononuclear cells (PBMC). Out of 71 CTCL cases, the clone was identified in 23 (32%). We identified the following clones: 1 V beta 3.1 (16MF), 7 V beta 5.1 (1 CD8+ CTCL, 1 CTCL not classified, 1 MF, 1 PA, 3 SS), 1 V beta 6.7 (1 SS), 7 V beta 8.1/8.2 (2 CTCL not classified, 1 PLEO, 2 MF, 2 SS), 1 V beta 12.1 (1 PLEO), 3 V beta 17.1 (2 CTCL not classified, 1 MF), 2 V beta 22.1 (1 CTCL not classified, 1 MF), 1 TCR delta (SS). The frequency of the malignant clone V beta usage corresponded well to the repertoire of V beta in eczematous skin but not to the repertoire in PBMC. In 6 patients, the malignant clone was mainly localized in the epidermis. In 17 cases, the clone-specific cells were distributed in epidermis and dermis equally. A retrospective analysis showed that preferential epidermal homing of the clone was associated with a non-aggressive clinical course. The V beta usage of CTCL and eczema suggests a special cutaneous microenvironment which might be co-created by certain (bacterial?) superantigens. A preferential epidermal homing of the clone might have prognostic implications.