Put Me in Your Shoes: Does Perspective-Taking Inoculate Against the Appeal of Alternative Partners?

People commit to monogamous relationships with the intent of maintaining sexual exclusivity but often fail to do so. Existing research has focused on individual and relationship characteristics that render relationships more vulnerable to infidelity, paying less attention to strategies that decrease the likelihood of straying. Three experiments investigated the impact of one strategy that might encourage people to enact relationship-protective responses toward alternative partners, perspective-taking. In all studies, participants either adopted the perspective of their partner or not and then evaluated, encountered, or thought about attractive strangers, in Studies 1-3, respectively. Participants' pro-relationship orientation and reactions during these experiences (interest in alternative and current partners, commitment to current relationships, and fantasmatic themes) were recorded. Results showed that perspective-taking decreased sexual and romantic interest in alternatives, while increasing commitment and desire for current partners. These findings suggest that partner perspective-taking discourages engagement in behaviors that may hurt partners and damage the relationship with them.

A lock-in thermal imaging setup for dermatological applications.

BACKGROUND: Lock-in thermal imaging is a thermographic method that is widely used in the nondestructive testing of materials. The technique allows detecting under the sample surface, small variations of the thermophysical properties in a noninvasive and noncontact manner. Surprisingly, this method has, to our knowledge, never been used in dermatology although it is particularly suited. METHODS: We present in this article the first lock-in thermal imaging setup dedicated to dermatological applications. The apparatus uses a temperature-modulated airflow to periodically stimulate the skin surface. The infrared images recorded by a high sensitive camera are demodulated according to the digital lock-in principle to compute a phase and amplitude image. RESULTS: First results obtained on benign skin lesions are presented. The images allow to detect small variations of the tissue thermophysical properties like for example, perfusion variations. Lock-in thermal imaging has the ability to reject disturbing thermal signals coming from subcutaneous tissues. The localization of the lesions is more accurate due the suppression of the lateral heat spreading. CONCLUSION: Lock-in thermal imaging is a promising method for the detection of lesions exhibiting modified thermophysical properties compared to the surrounding healthy skin.

Pruritic acquired nevus of Ota.

Nevus of Ota is a unilateral, asymptomatic cutaneous and mucosal hyperpigmentation of the face that is congenital or may appear during childhood. We present a case of symptomatic acquired nevus of Ota in an adult, associated with intense pruritus, not described in the literature so far. A 32-year-old woman presented with brownish mottled macules which appeared on her face progressively over 8 days, following the distribution of the first and second divisions of the left trigeminal nerve and partially covering the iris and sclera of the left eye. She reported an intense pruritus in this area. We performed a biopsy on the left forehead, which confirmed the diagnosis of nevus of Ota. Specific stains and immunohistochemistry revealed increased numbers of mast cells. Ophthalmological tests showed acute acquired melanocytosis of the left iris and sclera. The origin of the nevus is still unclear. Several hypotheses suggest a reactivation of melanocytes during their migration from the neural crest. The pruritus reported in our patient may be explained by the increased quantity of mast cells observed in the lesion and/or neuronal stimulation of the ophthalmic and maxillary divisions of the fifth cranial nerve.

[Lentigo maligna: a special melanoma]. / Lentigo maligna: un mélanome particulier.

Lentigo maligna (LM) and lentigo maligna melanoma (LMM) account for about 10% of all melanomas. They have distinct clinical and histological features as well as specific epidemiology, natural history, evolution, and genetics. Epidemiology of these tumors progressively concerns younger patients. Diagnostic and preparation of surgical removal of LM and LMM can now be optimized by new technologies of imaging, like dermoscopy or in vivo confocal reflectance microscopy. Surgery is the treatment of choice, but alternative options can be considered, especially for the elderly for whom the needs for efficiency and acceptability should be met.

[Scleroedema adultorum Buschke in a diabetic subject: intravenous immunoglobulin therapy]. / Scléroedème de Buschke chez un diabétique: traitement par immunoglobulines intraveineuses.

BACKGROUND: Scleroedema adultorum Buschke (SB) is a rare disease involving scleroedema of the neck and shoulders. It can extend to the rest of the trunk and the limbs but characteristically spares the extremities. Three types of SB are distinguished: the first is acute and develops after an infectious disease, the second is of insidious evolution and is associated with monoclonal gammopathy, and the third is associated with type 2 diabetes. PATIENTS AND METHODS: We report the case of a type 2 diabetic patient presenting with progressive, oedematous timbering of the trunk associated with impaired mobility, dysphagia and restrictive respiratory syndrome. SB was diagnosed on the basis of clinical presentation and histology. Treatment was mandatory because of the adverse impact of the disease. A therapy that would not worsen the patient's comorbidities had to be chosen. Intravenous immunoglobulins were thus initiated with excellent response as of the first cycle regarding trunk mobility and dysphagia. Cutaneous rigidity improved steadily until the end of treatment (eight cycles). CONCLUSION: Therapeutic abstention is the rule in SB if it has no severe functional repercussions. Nevertheless, there is no clearly indicated treatment once therapy becomes necessary. Control of underlying diabetes usually does not improve the scleroedema and the metabolic syndrome contraindicates most of the treatments reported in the literature. In this article, we suggest a new treatment of SB in the diabetic patient.

[Follow-up of melanoma lesions]. / Surveillance des lésions mélanocytaires.

Due to the early diagnosis, melanomas can be diagnosed in early stages. Most melanomas tend not to show morphological criteria of malignancy in the very early stages. They rather resemble benign moles. For patients with hundreds of atypical lesions, follow-up examinations using digital dermoscopy are very helpful. This technique enables the physician to monitor lesions and to detect microscopic change. Lesions with microscopic change are thought to be high risk lesions and should be removed this will represent important savings for the health system because this will allow to make the diagnosis of melanoma in earlier stages and to save costs for unnecessary surgery. In this article we are going to review the technique.

[Cancer and fecundity]. / Cancer et fécondité.

The overall increase in relative survival rates of adult and childhood cancer patients is related to improved chemotherapy and radiotherapy treatment protocols. However, this success is tempered by gonadotoxic effects and uterine damage. The reduced fertility and possible premature menopause can have a profound impact on patients self-esteem and quality of life. Consequently, preservation of fertility or treatments to protect the ovarian function, become a more relevant issue. Advances in assisted reproduction techniques have focused on the following: embryo cryopreservation which is restricted by time and constrains such as, sexual maturity and the presence of a stable partner. Cryopreservation of immature ovarian tissue, the most promising option, with restoration of natural fertility following auto-transplantation or maturation of oocytes in vitro in combination with assisted reproduction.

Direct evidence to support the role of antigen-specific CD8(+) T cells in melanoma-associated vitiligo.

Vitiligo is a cutaneous pigmentary disorder characterized by the loss of melanocytes. An autoimmune mechanism is strongly suspected to be involved in this affection given that it is frequently associated with autoimmune hormonal disorders, and because antibodies directed against melanocytic antigens are found in the serum of patients with vitiligo. We examined the role of cellular immunity in melanoma-associated vitiligo by expanding infiltrating lymphocytes from fresh biopsy specimens of vitiligo patches in melanoma patients. The vitiligo-infiltrating lymphocytes were almost exclusively T lymphocytes, and most were CD8(+). Following in vitro expansion, vitiligo-infiltrating lymphocytes remained predominantly CD8(+) and expressed the cutaneous homing receptor CLA. Furthermore, vitiligo-infiltrating lymphocytes had a clonal or oligoclonal T cell receptor profile, possibly reflecting specific antigenic stimulation. Finally, vitiligo- infiltrating lymphocytes specifically recognized differentiation antigens shared by normal melanocytes and melanoma cells. This direct demonstration of CD8(+) T cell involvement in vitiligo suggests that, in melanoma patients, vitiligo may be a visible effect of a spontaneous antitumoral immune response.

Melanoma peptide MART-1(27-35) analogues with enhanced binding capacity to the human class I histocompatibility molecule HLA-A2 by introduction of a beta-amino acid residue: implications for recognition by tumor-infiltrating lymphocytes.

The design of heteroclytic antigens with high MHC binding capacity is of particular interest to overcome the weak immunogenicity of peptide epitopes derived from tissue antigens expressed by tumors. In the present study, double-substituted peptide analogues of the tumor-associated antigen MART-1(27-35) incorporating a substitution at a primary anchor residue and a beta-amino acid residue at different positions in the sequence were synthesized and evaluated for binding to the human histocompatibility class I molecule HLA-A2 and for recognition by tumor-infiltrating lymphocytes. Interestingly, by combining a Leu for Ala substitution at P2 (which alone is deleterious for antigenic activity) with a beta-amino acid substitution at a putative TCR contact residue, recognition by tumor-infiltrating lymphocytes was partially restored. The analogue [Leu(28),beta-HIle(30)]MART-1(27-35) displays both a higher affinity to HLA-A2 and a more prolonged complex stability compared to [Leu(28)]MART-1(27-35). Overall, these results suggest that double-substitution strategies and beta-amino acid replacements at putative TCR contact residues might prove useful for the design of epitope mimics with high MHC binding capacity.

Longitudinal follow-up of cellular and humoral immunity induced by recombinant adenovirus-mediated gene therapy in cancer patients.

Replication-defective adenoviruses are arousing growing interest as both gene therapy and vaccine vectors. In a phase I clinical trial designed to evaluate the feasibility and tolerance of recombinant adenovirus (rAd)mediated gene transfer, we previously demonstrated that a single intratumoral injection of 10(9) PFU of rAd encoding the beta-galactosidase protein (Ad-beta-Gal) induced strong short-term (1-3 months) humoral, helper (Th1 type) and cytotoxic T cell responses specific for the transgene product in patients with advanced lung cancer. The purpose of the present study was to evaluate the persistence of long-lasting immunity to the transgene protein and in parallel, to assess patient immunocompetence revealed by responses to recall antigens (tetanus toxoid, purified protein derivative), viral pathogens (Epstein-Barr virus, influenza virus), and allogeneic antigens in mixed lymphocytic reactions. The beta-Gal-specific proliferative response declined rapidly in patients with progressive disease, as did responses to the other antigens. In contrast, a long-lasting proliferative response to beta-gal was maintained in an immunocompetent patient in complete remission 2 years after an injection of 108 PFU of Ad-beta-Gal. Anti-beta-Gal humoral (IgG and IgA) responses persisted notably, as did responses to TT and poliomyelytic antigens. While T cell effector cytotoxic responses specific for the viral peptides plummeted, the frequency of anti-beta-Gal CTL precursors remained particularly high, thus attesting to major immunization. Despite the impact of both advanced disease and chemotherapy on immunocompetence, we show the long-term persistence of immunity to the transgene protein vectorized by rAd.

Development of vitrified matured cattle oocytes after thawing and culture in vitro.

Bovine oocytes were partly denuded either at the beginning (t0) or six hours (t6) after the beginning of maturation and vitrified by the open pulled straw method at the end of the maturation process. After warming and fertilisation, their development in vitro and in vivo was assessed. The rates of production of blastocysts achieved in vitro were 3.4 per cent for the t0 group and 0.9 per cent for the t6 group compared with 40.4 per cent for the control oocytes. After transfer at the blastocyst stage pregnancies have been established in the three groups. Some of these pregnancies originated from vitrified oocytes which were further vitrified at the blastocyst stage before being transferred into synchronised recipients.

Phylogenetic analyses indicate an atypical nurse-to-patient transmission of human immunodeficiency virus type 1.

A human immunodeficiency virus (HIV)-negative patient with no risk factor experienced HIV type 1 (HIV-1) primary infection 4 weeks after being hospitalized for surgery. Among the medical staff, only two night shift nurses were identified as HIV-1 seropositive. No exposure to blood was evidenced. To test the hypothesis of a possible nurse-to-patient transmission, phylogenetic analyses were conducted using two HIV-1 genomic regions (pol reverse transcriptase [RT] and env C2C4), each compared with reference strains and large local control sets (57 RT and 41 C2C4 local controls). Extensive analyses using multiple methodologies allowed us to test the robustness of phylogeny inference and to assess transmission hypotheses. Results allow us to unambiguously exclude one HIV-positive nurse and strongly suggest the other HIV-positive nurse as the source of infection of the patient.

Cryopreservation of cattle oocytes: effects of meiotic stage, cycloheximide treatment, and vitrification procedure.

Different parameters likely to influence the survival of bovine oocytes after a vitrification procedure were evaluated: oocyte meiotic stage, cycloheximide treatment at the beginning or the end of maturation, and three vitrification procedures using conventional straws, open pulled straws (OPS), or microdrops. For each procedure a mixture of cryoprotectants (25% ethylene glycol and 25% glycerol) was used. After the oocytes were warmed and subjected to in vitro maturation and fertilization, the number that developed into blastocysts was determined. Results show that cryoprotectant exposure reduced embryo development and that cycloheximide treatment had no beneficial effect on oocytes vitrified in conventional straws. Among the three vitrification procedures, only the OPS method yielded blastocysts (approximately 3% of vitrified oocytes) irrespective of their initial meiotic stage. This result highlights the major influence of the cooling rate in an oocyte vitrification protocol.

HLA-G-mediated inhibition of antigen-specific cytotoxic T lymphocytes.

In the present study, we demonstrate that the non-classical MHC class I molecule HLA-G impairs specific cytolytic T cell functions in addition to its well-established inhibition of NK lysis. The antigen-specific cytotoxic T lymphocyte (CTL) response analyzed was mediated by CD8(+) T cells specific for the influenza virus matrix epitope, M58-66, presented by HLA-A2. The transfection of HLA-G1 cDNA in target cells carrying the M58-66 epitope reduced their lysis by these virus-specific CTL. This HLA-G-mediated inhibition of antigen-specific CTL lysis was (i) peptide dose dependent, (ii) reversed by blocking HLA-G with a specific mAb and (iii) still observed despite the blockade of HLA-E/CD94/NKG2A interaction. By inhibiting both CTL and NK functions, HLA-G appears to have an extensive role in immune tolerance.

Heterogeneity of HLA-G gene transcription and protein expression in malignant melanoma biopsies.

Nonclassical MHC class I HLA-G antigen expression is tissue specific and is thought to play a role in tolerance of the semiallogeneic fetus by the maternal immune system. Ectopic expression of HLA-G by tumor cells provides them with an additional mechanism of escape from immunosurveillance by host cytotoxic effector mechanisms. The aim of this study was to assess the expression of nonclassical HLA-G antigens in ex vivo human melanoma biopsies. HLA-G mRNA levels corresponding to both membrane-bound and soluble protein isoforms were analyzed in tumor specimens obtained from primary or metastatic melanomas of 23 patients. High levels of HLA-G transcription were detected in tumor specimens in 5 of 23 patients and found to be comparable in both lymph node and skin metastases. HLA-G mRNA transcript levels at tumor sites in 18 of these patients were compared with those in samples of their own healthy skin and were higher in the tumor tissue in 12 patients. Differential expression of mRNA transcripts corresponding to soluble and membrane-bound HLA-G was also observed in some tumor biopsies. HLA-G protein expression was detected in tumors that exhibited high levels of HLA-G transcription by immunofluorescence of frozen sections and Western blot analysis of both tumor and healthy skin biopsies, using anti-HLA-G-specific monoclonal antibodies. This work provides evidence that HLA-G gene transcription and protein expression can be up-regulated ex vivo in melanoma. Our finding that several of the tumors studied expressed high levels of HLA-G provides additional clues as to how a tumor can be selected in vivo to escape from cytotoxic antitumor responses, constituting a new parameter to be considered in the design of therapeutic approaches aimed at enhancing antitumor immune responses.

HLA-G expression in melanoma: a way for tumor cells to escape from immunosurveillance.

Considering the well established role of nonclassical HLA-G class I molecules in inhibiting natural killer (NK) cell function, the consequence of abnormal HLA-G expression in malignant cells should be the escape of tumors from immunosurveillance. To examine this hypothesis, we analyzed HLA-G expression and NK sensitivity in human malignant melanoma cells. Our analysis of three melanoma cell lines and ex vivo biopsy demonstrated that (i) IGR and M74 human melanoma cell lines exhibit a high level of HLA-G transcription with differential HLA-G isoform transcription and protein expression patterns, (ii) a higher level of HLA-G transcription ex vivo is detected in a skin melanoma metastasis biopsy compared with a healthy skin fragment from the same individual, and (iii) HLA-G protein isoforms other than membrane-bound HLA-G1 protect IGR from NK lysis. It thus appears of critical importance to consider the specific role of HLA-G expression in tumors in the design of future cancer immunotherapies.

Generation of Melan-A/MART-1-specific CD8+ cytotoxic T lymphocytes from human naive precursors: helper effect requirement for efficient primary cytotoxic T lymphocyte induction in vitro.

This study investigates the generation of primary melanoma cell-specific cytotoxic T lymphocytes (CTLs) in vitro. Induction of peptide-specific CTLs from unfractionated naive peripheral blood mononuclear cells from HLA-A2 healthy donors was assessed using 2 recently described 9-mer epitopes from the melanoma tumor antigen Melan-A/MART-1. The need for help from CD4+ T lymphocytes for the long-lasting induction of CTLs and the capacity of the peptide-induced CTL lines to recognize many melanoma cells were evaluated. CTL lines were obtained reproducibly when CD4+ T-lymphocyte help was provided during the primary stimulation either in an autologous way, in the case of tetanus toxoid antigen (TT) responder donors, or with allogeneic TT-activated T-helper cells, separated by an insert well, in the case of tetanus toxoid non-responder donors. We also investigated helper T-cell-derived factors that are produced by TT-activated lymphocytes. Our results strongly suggest that a complex network of cytokines like interleukin-2 (IL-2), interferon-gamma, IL-6 and IL-1 exerts stimulatory effects for the initiation process of CTLs. In contrast, cytokine-like IL-4 might inhibit generation of cytolytic activity if provided by TT-activated T cells at early stages of induction. Our approach can be used to generate CTLs of a desired specificity for clinical use in adoptive immunotherapy protocols.

[Gilbert disease and isotretinoin]. / Maladie de Gilbert et isotrétinoïne.

INTRODUCTION: Because of the potential hepatotoxicity of retinoids, prescription of isotretinoin is always very carefully made in healthy subjects, and prohibited in case of concomitant hepatopathy. Gilbert's syndrome consists of chronic, mild, unconjugated hyperbilirubinemia. In this syndrome, isotretinoin has been reported twice to be perfectly tolerated, and once even beneficial. We report here a new case of good tolerance and even improvement of a Gilbert's syndrome during isotretinoin therapy. CASE REPORT: A 17-year-old man with Gilbert's syndrome presented with a nodulocystic acne. Topical agents had been inefficient, and cyclines bad tolerated. Thus isotretinoin has been gradually introduced, with a regular monitoring of the liver function. We observed a steady decrease of the bilirubinemia during the course of isotretinoin, and then a reappearance of hyperbilirubinemia as soon as posology was diminished and particularly after completion of isotretinoin therapy. DISCUSSION: A review of the literature finds only very few cases of hepatic injuries caused by isotretinoin, contrary to etretinate. Safety of isotretinoin in Gilbert's syndrome was first observed in 1984, but its beneficial effects have only recently been described by Wang et al., and we report here a similar case. Pharmacological mechanisms remain hypothetic. However, considering the prevalence of Gilbert's syndrome and its usual first expression during postpubertal period, it seems to us interesting for therapeutic practice to know that isotretinoin is not less safe in these patients.