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Biomedical subjects

J H Saurat

Publications and source records attributed to J H Saurat.

At least 19 recordsLinked to original sources
PubMed2006

Intralesional and intravenous treatment of cutaneous B-cell lymphomas with the monoclonal anti-CD20 antibody rituximab: report and follow-up of eight cases.

BACKGROUND: Rituximab (MabThera); Roche, Basel, Switzerland; an anti-CD20 chimeric monoclonal antibody) has been shown to have significant activity in nodal B-cell lymphomas, with few associated adverse effects. Its efficacy and safety were first demonstrated in the treatment of systemic B-cell lymphomas. Intravenous and subsequently intralesional administration of rituximab have also been reported to be effective and well tolerated in cutaneous B-cell lymphoma (CBCL). The comparative efficacy of intravenous vs. intralesional rituximab in CBCL is not known. OBJECTIVES: To evaluate the objective response rate, relapse rate, time to progression, and tolerance in patients with CBCL treated with intravenous or intralesional rituximab. METHODS: Eight patients with multiple primary CBCL (four follicle centre lymphoma and four marginal zone lymphoma) were treated with intralesional rituximab (six patients; 10-30 mg per lesion, three times weekly for one or two cycles at a 4-week interval) or intravenous rituximab (two patients; 375 mg m(-2) once weekly for four consecutive weeks). RESULTS: Complete clinical remission was obtained in all cases. The two patients treated intravenously did not relapse during a follow-up period of 18-24 months. Four of six patients treated intralesionally presented a relapse of new lesions at another site within a mean of 6 months after treatment. The injected lesions did not, however, recur. New lesions also responded to another cycle of intralesional rituximab. Tolerance to treatment was very good in both treatment groups. CONCLUSIONS: Rituximab therapy of CBCL appears to have a potential advantage in cases where lesions are localized in sites that are difficult to treat with radiotherapy or surgery and in which secondary scarring or alopecia is likely. Intralesional injections of rituximab allow the use of considerably smaller doses compared with intravenous treatment, with similar response rates and tolerance. However, within a 12-month follow-up period, relapse of CBCL with new lesions at distinct sites was frequently observed after intralesional treatment.

Adult↗
PubMed2002

[Dermatoscopy of pigmented lesions].

Dermoscopy is a simple to use in vivo method for the early diagnosis of malignant melanoma and the differential diagnosis of pigmented skin lesions. It has been shown to increase diagnostic accuracy over clinical visual inspection in the hands of an experienced physician. This paper is a review of the principles of Dermoscopy as well as recent technological developments.

Algorithms↗
PubMed2001

The hemidesmosomal protein bullous pemphigoid antigen 1 and the integrin beta 4 subunit bind to ERBIN. Molecular cloning of multiple alternative splice variants of ERBIN and analysis of their tissue expression.

The bullous pemphigoid antigen 1 (eBPAG1) is a constituent of hemidesmosomes (HDs), cell-substrate adhesion complexes in stratified epithelia. Although its COOH terminus interacts with intermediate filaments, its NH(2) terminus is important for its recruitment into HDs. To identify proteins that interact with the NH(2) terminus of human eBPAG1, we performed a yeast two-hybrid screen, which uncovered a protein belonging to the LAP/LERP (for LRR and PDZ domain) protein family with 16 NH(2)-terminal leucine-rich repeats and a COOH-terminal PDZ domain. The gene for this LAP/LERP protein comprises at least 26 exons located on the long arm of chromosome 5. In most human tissues, several transcripts were detected differing in the coding region situated upstream of or within the PDZ domain. One of the encoded variants was found to correspond to the recently described protein ERBIN. In yeast and in vitro binding experiments, ERBIN was shown to interact not only with eBPAG1 but also with the COOH-terminal region of the cytoplasmic domain of the integrin beta4 subunit, another component of HDs. Antibodies raised against the COOH terminus showed that ERBIN is expressed in keratinocytes. In transfected epithelial cells the protein, however, was not localized in HDs but was either diffusely distributed over the cytoplasm or concentrated at the basolateral plasma membrane. Because ERBIN had been shown previously to interact with the transmembrane tyrosine kinase receptor Erb-B2, which in turn associates with the integrin beta4 subunit, we suggest that ERBIN provides a link between HD assembly and Erb-B2 receptor signaling.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Selective expression of FLIP in malignant melanocytic skin lesions.

FLIP (FLICE Inhibitory Protein) is a recently identified intracellular inhibitor of caspase-8 activation that potently inhibits cell death mediated by all death receptors including Fas and TRAIL. FLIP has recently been shown to favor tumor growth and immune escape in mouse tumor models. We analyzed FLIP expression by immunohistochemistry in a panel of 61 benign and malignant human melanocytic skin lesions. FLIP expression was undetectable in all but one benign melanocytic lesion (31/32, 97%). In contrast, FLIP was strongly expressed in most melanomas (24/29 = 83%). Overexpression of FLIP by transfection in a Fas- and TRAIL-sensitive human melanoma cell line rendered this cell line more resistant to death mediated by both TRAIL and FasL. Selective expression of FLIP by human melanomas may confer in vivo resistance to FasL and TRAIL, thus representing an additional mechanism by which melanoma cells escape immune destruction.

Antibody Specificity↗
PubMed2001

Plectin, an unusual target antigen in bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is a blistering disease associated with autoantibodies directed against two components of hemidesmosomes, BP180 and BP230. OBJECTIVES: To assess whether BP patients have autoantibodies targeting plectin, another hemidesmosomal component showing extensive homology to BP230. METHODS: Examination of sera from 16 patients with BP, using immunoprecipitation studies followed by immunoblotting. RESULTS: Serum of one of the 16 (6%) patients with BP contain autoantibodies binding to plectin, while no reactivity was found with sera from three control subjects. Sera from all 16 BP patients immunoprecipitated BP230 from extracts of biosynthetically radiolabelled human keratinocytes. CONCLUSIONS: Our results indicate that sera from BP patients might contain autoantibodies binding to plectin. Although this protein and BP230 are closely sequence-related, the occurrence of autoantibodies binding to plectin is a rare phenomenon in BP.

Autoantibodies↗
PubMed2001

Autoantibodies to the extracellular and intracellular domain of bullous pemphigoid 180, the putative key autoantigen in bullous pemphigoid, belong predominantly to the IgG1 and IgG4 subclasses.

BACKGROUND: Autoantibodies to the extracellular domain (ECD) of bullous pemphigoid (BP) antigen 180 (BP180) are thought to play a crucial part in the pathophysiology of BP. OBJECTIVES: As the various IgG subclasses have different biological properties, we have sought to assess the relative isotype distribution of IgG to BP180 and their reactivity against the ECD and intracellular domain (ICD) of BP180. METHODS: The reactivity of 27 sera from patients with BP was assayed by immunoblotting against recombinant proteins covering the ECD and ICD of BP180. RESULTS: Twenty-seven (100%) and 21 (77%) of 27 BP sera, respectively, contained IgG1 and IgG4 autoantibodies binding to the ECD of BP180. Fourteen (82%) and six (35%) of the 17 BP sera that were reactive with the ICD of BP180 had autoantibodies of the IgG1 and IgG4 subclass, respectively. The profile of the isotype restriction appeared to be similar when the response to the ECD vs. that to the ICD was compared. IgG2 and IgG3 reactivity with BP180 was found less frequently. Patients with BP of longer duration showed a tendency to have, in addition to IgG1, an IgG4 response. CONCLUSIONS: Consistent with prior evidence indicating that subepidermal blister formation in BP is dependent upon complement activation, the frequent finding of complement-fixing IgG1 autoantibodies to both the ECD and ICD of BP180 might have pathogenic relevance in BP. These findings provide new insights relevant for our understanding of the immune response to BP180, the putative key autoantigen in BP.

Aged↗
PubMed2001

Skin, sun, and vitamin A: from aging to cancer.

Human epidermis contains significant amounts of Vitamin A, the enzymes responsible for its metabolism toward either storage or activation, the binding proteins for its protection and specific transport, and the nuclear receptors involved in the vitamin A-induced gene-activity modulation. This complex system may be drastically altered upon ultraviolet light exposure because vitamin A absorbs in the UVB range. We have conducted a series of experiments in order to analyse the effects of UV exposure on the epidermal stores of endogenous vitamin A (retinol and retinyl esters), the activity of enzymes and binding proteins, and some biological parameters such as apoptosis transcription factors expression (cJun) and thymine dimers. Current data indicate that the vitamin A system is a direct target of both UVB and UVA and participates in an adaptive response to UV exposure. The physiological role of this adaptive response to acute and chronic sun exposure should be further analysed. Interfering with this UV-induced vitamin A deficiency is a new concept for the prevention of skin cancer and aging.

Animals↗
PubMed2001

Chronic borreliosis presenting with morphea- and lichen sclerosus et atrophicus-like cutaneous lesions. a case report.

We report on a case of chronic cutaneous borreliosis with manifestations clinically compatible with morphea and lichen sclerosus et atrophicus. The histopathologic features of these lesions were those of acrodermatitis chronica atrophicans. Our case illustrates the concept that clinical aspects of morphea and lichen sclerosus et atrophicus pertain to the spectrum of cutaneous borreliosis.

Abdomen↗