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BACKGROUND: Vitiligo is an acquired dermatological condition that is characterized by depigmentation of patches of skin. It is relatively common, occuring in about 0.38-0.50% of the general population, and can engender significant cosmetic disfigurement and psychological sequelae in the affected individual. Recent studies demonstrate that topical tacrolimus (Protopic; Astellas, Markham, ON, Canada) is efficacious in the treatment of vitiligo. We propose that the successful treatment of vitiligo with topical tacrolimus involves the unique immunosuppressive actions of the T lymphocyte T-helper (Th) 2 cytokine, interleukin (IL)-10. OBJECTIVES: We aimed to monitor clinical changes in lesions of vitiligo treated with topical tacrolimus 0.1% ointment and quantify IL-10 cytokine levels in nonvitiliginous skin, as well as lesions of vitiligo before and following topical tacrolimus therapy. METHODS: Clinical evaluation of lesions of vitiligo on the basis of surface area and follicular repigmentation under Wood's lamp was performed in 20 enrolled adult patients. Biopsy specimens were obtained from nonvitiliginous skin, as well as lesions of vitiligo before and following topical tacrolimus therapy. Specimens were processed and analysed for expression of IL-10 using the method of enzyme-linked immunosorbent assay. RESULTS: A statistically significant mean +/- SEM decrease in vitiligo lesion size of 41.0 +/- 5.2% was observed following 3 months of treatment. A pattern of follicular repigmentation was noted by the third month of treatment for all patients completing the study. In addition, there was a statistically significant difference between IL-10 expression in vitiligo lesions following treatment for 3 months with topical tacrolimus compared with untreated vitiligo lesions (P = 0.017) and normal skin (P = 0.004). CONCLUSIONS: These results confirm that topical tacrolimus is an effective treatment for vitiligo. We propose that topical tacrolimus increases IL-10 expression in vitiligo lesions, and thereby inhibits melanocyte destruction triggered by unchecked Th1 pathways in vitiligo.

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Pg is a homologue of beta-catenin and Armadillo, the product of the Drosophila segment polarity gene and has been shown to have both adhesive and signaling functions. It interacts with both classic and desmosomal cadherins. Pg interaction with the desmosomal cadherins is essential for desmosome assembly. Its precise role in the classic cadherin complexes is unclear, although Pg-E-cadherin interaction appears to be necessary for the formation of desmosomes. In addition to cadherins in adhesion complexes, Pg interacts with a number of proteins involved in regulation of cell differentiation and proliferation such as Lef-1/Tcf-1 transcription factors and the tumor suppressor protein APC. In this study, we have introduced Pg cDNA into SCC9 cells, a Pg- and E-cadherin-deficient squamous cell carcinoma line, which also lacks desmosomes. These cells have both alpha-catenin and beta-catenin, display unusual expression of N-cadherin, and have the typical fibroblastic phenotype of transformed cells. Pg-expressing SCC9 cells (SCC9P) formed desmosomes. Desmosome formation coincided with the appearance of an epidermoid phenotype, with increased adhesiveness and a contact-dependent decrease in growth. Biochemical characterization of SCC9P cells showed an increase in the expression and stability of N-cadherin and a decrease in level and stability of beta-catenin, without any apparent effects on alpha-catenin. These results show that, in the absence of E-cadherin, Pg can efficiently use N-cadherin to induce desmosome formation and epidermoid phenotype. They also suggest a role for Pg as one of the regulators of the intracellular beta-catenin levels and underscore the pivotal role of this protein in regulating cell adhesion and differentiation.

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Terbinafine is an allylamine antifungal agent widely used to treat dermatophyte onychomycosis and dermatomycoses. We report 10 severe cutaneous adverse reactions associated with terbinafine therapy which required discontinuation of the antifungal agent: erythema multiforme (five patients), erythroderma (one), severe urticaria (one), pityriasis rosea (one) and worsening of pre-existing psoriasis (two patients). The spectrum of cutaneous adverse effects associated with terbinafine therapy is reviewed. Patients should be counselled about discontinuing terbinafine at the onset of a cutaneous eruption and about seeking medical advice about further management.

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SCC9 cells, derived from a squamous carcinoma of the tongue, were shown to lack E-cadherin but express alpha- and beta-catenins and N-cadherin. These cells also lack plakoglobin expression, do not assemble desmosomes and exhibit the typical morphology and growth properties of transformed cells. The N-cadherin expressed in SCC9 cells has properties similar to other classical cadherins, including interactions with the catenins. We transfected SCC9 cells with a full-length cDNA for L-CAM (liver cell adhesion molecule), the functional chicken homologue of E-cadherin. The exogenously expressed L-CAM formed complexes with catenins and the cytoskeleton and induced a morphological transition from fibroblastoid to epithelioid, conferred density-dependent growth inhibition, increased aggregation ability, and increased synthesis and stability of alpha- and beta-catenins. Coincident with these phenotypic changes, we detected a significant reduction in the level of endogenous N-cadherin, primarily as a result of rapid degradation of this protein in L-CAM-expressing cells. These results show the abnormal expression of N-cadherin in these transformed epidermoid cells, demonstrate the dynamics of the relationship between two cadherins, and provide a model system for the functional analysis of the tumor suppressor activity of E-cadherin in carcinomas.

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Psychosocial rehabilitation often remains entrapped within a restrictive definition. It is characterized by a normative orientation, which predetermines the objectives to achieve, and by an approach from outside of the person, which emphasizes the functional aspects of rehabilitation. In this context, marks of withdrawal, lack of involvement, or inactivity are interpreted as signs of passivity or as residual or negative symptoms, which are often associated with a negative prognosis. In parallel, as data regarding the heterogeneity of evolution of schizophrenia begin to accumulate, some authors have defended the idea that studies have to concentrate on the course of the disorder and on the associated processes (Harding et al. 1987; Strauss 1986). They propose going beyond an objective evaluation of signs and behaviors in order to situate them within a larger life-frame. This draws attention to the potential polysemy of symptoms, including the so-called negative symptoms, which can reflect a diversity of influences and therefore possess various psychiatric meanings (Strauss 1989). Yet, the systematic study of "meaning" in psychiatry is still in its infancy and lacks clear conceptual and methodological points of reference (Strauss and Estroff 1989). On another hand, implications for rehabilitation of a meaning-centered approach to psychiatric symptoms have not been fully elaborated. An intensive study conducted in Montreal with patients diagnosed as schizophrenics sought to describe the factors and processes associated with different types of insertion in the community, and particularly to understand the rehabilitative strategies and the specific forms of being-in-the-world associated with an ability to remain in the community. Data collected through open-ended interviews were both quantitatively analyzed and subjected to content and qualitative analysis. The conceptual reference frame was derived from anthropology and from the European school of psychiatric phenomenology. Data indicate that non-rehospitalization is associated with a stance of "positive withdrawal" (Corin 1990); it is characterized by a position at a distance from social roles and social relationships, combined with various strategies for keeping more tenuous links with the social environment. The case study presented here illustrates the complex organization of these various elements in a given life-frame. It also demonstrates the role played by symbols and meanings in developing a new articulation of personal experience.

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The biosynthesis and biochemical characteristics of the 39,000 cell surface glycoprotein detected by Mab 41H.16 were investigated. Experiments utilizing tunicamycin, endoglycosidase H, endoglycosidase F and N-glycosidase F indicate that the mature molecule expressed at the cell surface is composed largely of N-linked oligosaccharides of both the complex and high mannose types. When synthesized in the presence of tunicamycin, the molecule appeared on the cell surface with a Mr of 32,000. Digestion with both endoglycosidase H and endoglycosidase F yielded a single band of Mr 37,000. Parallel experiments with N-glycosidase F revealed species of approx. 35,000 and 32,000. Synthesis in the presence of monensin yielded a 37,500 product. [3H]Glucosamine and [3H]mannose were incorporated into the molecule but no evidence for fucose incorporation could be found. Microheterogeneity of gp39 with respect to Mr and oligosaccharide structure was demonstrated by biosynthetic labelling and lectin chromatography. Biosynthetic pulse-chase labelling showed that the de novo synthesis of the 39,000 molecule occurs without detectable precursor formation. Results of temperature-dependent phase separation experiments were consistent with gp39 being an integral membrane protein. Two-dimensional electrophoresis showed heterogeneity of the isoelectric points associated with the N-linked oligosaccharides. Galactose oxidase/NaB[3H]4 labelling showed that a terminal sialic acid protects a galactose residue. All results are consistent with the conclusion that the gp39 molecule is an integral membrane glycoprotein composed of heterogeneous N-linked oligosaccharides of both the complex and high mannose types.

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This study, based on a sampling of people who were diagnosed schizophrenic, sought to describe the different types of positive and negative social réintégration. Research combined an anthropological approach with rigid discipline in the gathering of data. The authors examined réintégration from three points of view : social relations, social roles, and utilization of space and time (l'espace-temps). Data shows that people who are constantly rehospitalized feel marginalized and experience rejection, particularly with family and relatives, and that these feelings sharply contrast the relatively normative expectations concerning réintégration. In these cases, the patient's psychiatric environment tends to structure the reintegration process. However, people who have not been rehospitalized are characterized by a dominant type of réintégration that is best described as"posi-tive retreat" ("retrait positif). This characteristic is supported by various psychological, social and cultural hypotheses. Moreover, an intercultural perspective suggests that certain traits in North American societies tend to make people look down on "positive retreat" and view this form of readaptation as negative.

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This report describes the clinical and laboratory features of seven cases of acute leukemia associated with the 4;11 chromosomal translocation. All seven children had acute lymphoblastic leukemia by standard morphologic and cytochemical criteria. Leukemic blasts from six of seven patients were terminal deoxynucleotidyl transferase-positive. Immunologic phenotyping suggested the leukemias were of B cell origin; blasts from five patients expressed HLA-DR and p24 (CD-9 antibody), blasts from three patients expressed B4 (CD-19), and blasts from two patients expressed the common acute lymphoblastic leukemia antigen (CD-10). One patient's leukemic blasts contained cytoplasmic immunoglobulin. Analysis of DNA from four of five patients demonstrated additional evidence of B cell differentiation with heavy-chain immunoglobulin gene rearrangement. When DNA from the four patients with heavy-chain immunoglobulin gene rearrangement was analyzed, one patient's DNA demonstrated light-chain immunoglobulin gene rearrangement. However, flow cytometric analysis of blasts from three patients showed the simultaneous expression of the lymphoid-associated antigen B4 (CD-19) and the myeloid-associated antigen My-1 (X-Hapten). Electron microscopic examination of blasts from one patient that expressed both lymphoid- and myeloid-associated antigens demonstrated ultrastructural characteristics of both lineages. These findings suggest that acute leukemia with the t(4;11) abnormality has mixed lineage characteristics as a result of leukemogenesis in a multipotential progenitor cell or aberrant gene expression later in differentiation. Furthermore, serial analysis of karyotype, immunophenotype, and heavy-chain immunoglobulin genes revealed changes in these biologic markers over time, suggesting continued chromosome rearrangement and gene modulation after the leukemogenic event in cells with the t(4;11).

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The actual language on mental health in Quebec is founded on a série of premises that generally remain implicit or are introduced as postulates of "good will" with regard to reality. The authors want to question the significance and the real range of those premises by using a comparative analysis. Considering the concept of desinstitutionalization as used in different countries, they detect the ambiguities and the differences due to the context and to the postulates specific to each of those systems. Then, to elaborate our own premises, they utilize a decentralization method: with the help of their knowledge of other cultural ways of reacting to the problems of psychiatry-mental health, on the one hand in Africa, and on the other from data gathered in Quebec from psychiatric patients, ex-patients and friends. This twofold study leads them to express, compare and criticize what they introduce as the three main premises of mental health language in Quebec: to popularize psychiatric-mental health problems and to introduce a standardization of the people and a uniformity of structure in a field that remains very complex. A study of the theoretical character of this model, of its moralizing dimension and of the key-actors who contribute to its definition, allows them to describe the socio-historic context. The authors question the possibility of introducing a new dimension in our ways of thinking, management and action.

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Monoclonal antibody 41H.16 was produced by using the hybridoma methodology in the mouse system with cells from a patient with hairy cell leukemia as the immunogen. This antibody reacts with the majority of Slg+ cells in the peripheral blood and with all B lymphoblastoid cell lines. Reactivity with conventional Ig determinants, Fc or C3 receptors, has been excluded. The antibody reacted with cells from 68 patients with CLL but showed no reactivity with cells in 69 specimens from patients with non-T, non-B ALL. The apparent m.w. of the antigen detected by this antibody is approximately 39,000.

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The toxicity to mice of combinations of 1-beta-D-arabinofuranosylcytosine and 3-deazauridine was investigated. The drugs were administered daily i.p. on Days 1 to 5, each drug at 10 mg/kg body weight; these dosages are small fractions of the dosages at which 10% of the treated animals died when either drug was administered alone on the foregoing schedule. This drug combination was severely toxic when 3-deazauridine was administered 2 to 8 hr prior to 1-beta-D-arabinofuranosylcytosine; most mice treated in this way died within 3 days of the last treatment. Histological examination showed that severe damage to the small bowel mucosa resulted from treatment with the drugs in the above, lethal sequence. In contrast, treatments with this drug combination at the same dosages were tolerated when the two agents were administered simultaneously or when 1-beta-D-arabinofuranosylcytosine preceded 3-deazauridine. Under the latter conditions, small bowel mucosal injury was much less severe. Female mice were more sensitive to the toxic treatment regimen than were male mice and were protected against the latter when either the 3-deazauridine or the 1-beta-D-arabinofuranosylcytosine component was preceded by treatment with nitrobenzylthioinosine (100 mg/kg), a potent inhibitor of nucleoside transport.

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A technique is described to correct male pattern baldness by transferring a large, single, temporo-occipital flap after one delay.

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When incubated with 1-beta-D-arabinofuranosylcytosine (ara-C), RPMI 6410 cells formed a hitherto unrecognized ara-C metabolite, 1-beta-D-arabinofuranosylcytosine diphosphate choline. This compound was characterized by (a) chromatographic behavior, (b) chemical and enzymatic hydrolysis, (c) phosphorus content, and (d) incorporation of [5-3H]ara-C and [methyl-14C]choline. Formation of 1-beta-D-arabinofuranosylcytosine diphosphate choline by RPMI 6410 cells was enhanced in the presence of 3-deazauridine (DU) and was preceded by that of 1-beta-D-arabinofuranosylcytosine triphosphate. The antiproliferative effects of ara-C and DU toward RPMI 6410 cells were potentiated when the agents were present together. The anabolism of ara-C during a 24-hr interval of culture was markedly enhanced by the presence of DU; cellular concentrations of 1-beta-D-arabinofuranosylcytosine triphosphate and 1-beta-D-arabinofuranosylcytosine diphosphate choline were 5- and 15-fold higher than those in the absence of DU. This enhancement appears to be the basis of the potentiation of cytotoxicity resulting from combination of the agents. Pretreatment of RPMI 6410 cells with DU resulted in enhanced rates of cellular uptake of ara-C. ara-C uptake under these circumstances was blocked by the inhibitor of nucleoside transport, nitrobenzylthioinosine.

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1-beta-D-Arabinofuranosylcytosine diphosphate choline was formed from 1-beta-D-arabinofuranosylcytosine (ara-C) during incubation in vitro of peripheral myeloblasts from patients with acute myelogenous leukemia and cultured cells (nonleukemic human lymphocytes, mouse lymphoma L5178Y, and HeLa); as well, 1-beta-D-arabinofuranosylcytosine diphosphate choline was formed in vivo in mouse leukemia L1210 cells and mouse liver. 3-Deazauridine enhanced the anabolism of ara-C in nonleukemic lymphocytes in vitro and leukemia L1210 cells in vivo but did not influence ara-C anabolism in the other cell types. In acute myelogenous leukemia myeloblasts incubated in vitro with ara-C, concentrations of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate were maximal after 8 hr of incubation and formation of the latter preceded that of 1-beta-D-arabinofuranosylcytosine diphosphate choline.

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