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Biomedical subjects

M Duvic

Publications and source records attributed to M Duvic.

At least 91 records · Page 5Linked to original sources
PubMed1996

Combined modality therapy for cutaneous T-cell lymphoma.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) may respond to many therapies, but long-term disease-free survival is uncommon. Patients with advanced disease have a median survival of approximately 3 years. OBJECTIVE: Our purpose was to combine known effective agents sequentially to determine whether we could achieve remission in more patients or for longer duration. METHODS: Patients with mycosis fungoides (n = 23) or Sézary syndrome (n = 5) were treated with 4 months of recombinant interferon alfa together with isotretinoin, followed by total skin electron beam therapy alone (for stage I to II disease) or preceded by chemotherapy (for stage III to IV disease). Maintenance therapy consisted of interferon for 1 year and topical nitrogen mustard for 2 years. RESULTS: Twenty-eight patients were treated. The overall response rate (complete and partial remissions) was 82%. Although the median duration of remission was 5 months in patients with stage III to IV disease, two patients remain in complete remission at 39 + and 46 + months. In patients with stage I to II disease the median duration of remission has not been reached at a median follow-up of 18 months. Five patients, all with stage III to IV disease, have died. Overall, the regimen was well tolerated with one treatment-related death from neutropenic sepsis. CONCLUSION: Combined modality therapy may be effective for the treatment of CTCL with similar response rates to other current therapies.

Administration, Cutaneous↗
PubMed1996

False-positive polymerase chain reaction results for human papillomavirus in lichen planus. Potential laboratory pitfalls of this procedure.

BACKGROUND: The polymerase chain reaction (PCR) is a common tool in laboratory evaluation of tissue samples. It has been particularly useful in testing for nucleic acids of infectious organisms implicated in the pathogenesis of cutaneous diseases. OBJECTIVE: Our purpose was to evaluate archival biopsy material (paraffin-embedded) of lichen planus for human papillomavirus (HPV) DNA with PCR and in situ hybridization (ISH). METHODS: Tissue sections were obtained from 13 specimens of lichen planus and 10 control tissues. Standard methods for PCR and ISH were used to evaluate the presence of HPV DNA. RESULTS. Initial PCR results demonstrated HPV DNA in 11 of 13 specimens and in none of the control tissue. However, testing for specific HPV types revealed nucleic acid contamination. ISH was negative in all specimens. CONCLUSION: Accurate evaluation of tissue with PCR is difficult because of the procedure's profound sensitivity. Positive results reported in the literature should be viewed with caution. Potential causes for false-positive and false-negative results should be considered.

Biopsy↗
PubMed1996

A randomized trial of minoxidil in chemotherapy-induced alopecia.

BACKGROUND: Hair loss is a side effect of many chemotherapeutic agents, and patients have even refused possibly palliative or lifesaving drugs because they could not accept temporary or prolonged baldness. Topical minoxidil has been shown to be effective for androgenetic alopecia and alopecia areata. OBJECTIVE: Our purpose was to investigate the value and safety of minoxidil in chemotherapy-induced hair loss. METHODS: Twenty-two women who were facing adjuvant chemotherapy after breast surgery were registered in a protocol that used a 2% minoxidil topical solution or a placebo in a randomized double-blind trial. RESULTS: There was a statistically significant difference (favoring minoxidil) in the interval from maximal hair loss to first regrowth. Thus the period of baldness was shortened (mean, 50.2 days) in the minoxidil group. CONCLUSION: Minoxidil decreased the duration of alopecia caused by chemotherapy. There were no significant side effects.

Administration, Cutaneous↗
PubMed1996

Photopheresis therapy for cutaneous T-cell lymphoma.

BACKGROUND: Cutaneous T-cell lymphoma is a chronic peripheral lymphoma in which aggressive combined therapy elicits high response rates but does not improve survival. Photopheresis therapy has reportedly induced remissions and prolonged survival in patients with advanced disease. OBJECTIVE: We studied all patients who began photopheresis treatment between February 1988 and July 1994 to determine whether we could confirm the remission rates of previous studies, to evaluate variables that might predict a response, and to discover whether an accelerated delivery system would improve the remission rate or response time. METHODS: After an oral dose of methoxsalen was administered, a leukocyte-enhanced quantity of blood was exposed to UVA radiation for 1.5 hours and returned to the patient. With our accelerated system, 6 x 10(9) cells were irradiated in nine cycles. Treatments were given on 2 consecutive days once a month. RESULTS: Among 34 patients whose results could be evaluated, the overall response rate (complete and partial remissions) was 50%; most patients had mild side effects. All responders except one had erythroderma. Responders had a decrease of 75% in mean skin scores, whereas nonresponders had an increase of 21%. CONCLUSION: Photopheresis appears to be effective for selected patients with erythrodermic cutaneous T-cell lymphoma, although we did not achieve as high a remission rate as previously reported by others.

Adult↗
PubMed1996

Systemic lupus erythematosus diagnosed during interferon alfa therapy.

We describe a patient who had clinical manifestations of several autoimmune disorders: Sjögren's syndrome, benign hypergammaglobulinemic purpura of Waldenström, and systemic lupus erythematosus (SLE). The SLE was diagnosed during therapy with interferon alfa. Testing for anti-Ro and anti-La antibodies was negative until the serum was diluted to eliminate a possible prozone phenomenon of antibody excess.

Female↗
PubMed1996

Tazarotene-induced gene 1 (TIG1), a novel retinoic acid receptor-responsive gene in skin.

Retinoids exert their effect through ligand-dependent transcription factors, retinoic acid receptors (RARalpha, beta, and gamma) and retinoid X receptor (RXRalpha, beta, and gamma), which belong to the superfamily of steroid/thyroid/vitamin D3, nuclear receptors. Using a subtraction hybridization approach, we have identified a cDNA sequence, Tazarotene Induced Gene 1 (TIG1), which is highly upregulated in skin raft cultures by an RARbeta/gamma -selective retinoid AGN 190168 (tazarotene/ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)-ethynyl]nicotinate), which is effective in the treatment of psoriasis. The retinoid-mediated upregulation in the expression of TIG1 was confirmed by Southern and Northern analyses. Upon sequencing, TIG1 was found to be a novel cDNA which encodes a protein of 228 amino acids whose sequence suggests that is a transmembrane protein with a small N-terminal intracellular region, a single membrane-spanning hydrophobic region, and a large C-terminal extracellular region containing a glycosylation signal. We demonstrate that TIG1 is also upregulated by AGN 190168 in skin raft cultures prepared from psoriatic fibroblasts and normal keratinocytes and in primary fibroblast and keratinocyte cultures. We also show that TIG1 is upregulated by retinoic acid receptor but not by retinoid X receptor-specific synthetic retinoids. Finally, we demonstrate that TIG1 is induced by AGN 190168 in psoriatic lesions during the course of clinical treatment of the disease.

Amino Acid Sequence↗
PubMed1996

Localization of the Darier disease gene to a 2-cM portion of 12q23-24.1.

Positional cloning with microsatellite markers allowed further localization of the Darier disease gene to a 2-cM interval of chromosome 12, 12q23-24.1, between the polymorphic loci D12S234 and D12S129. A region this size is suitable for construction of a contig to identify the Darier disease gene. Use of a polymorphic intronic marker for nitric oxide synthetase 1 gene, which maps to the same chromosomal area as the Darier gene, allowed exclusion of that gene as the Darier disease gene.

Chromosome Mapping↗
PubMed1996

HLA-DR5 and DQB1*03 class II alleles are associated with cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) may present with eczematous lesions, mycosis fungoides (MF), or as exfoliative erythroderma with circulating atypical cells, Sezary syndrome (SS). The "malignant" T cells are epidermotropic and clonal, but whether they respond to antigen stimulation is unknown. Because CD4+ lymphocytes recognize antigen presented by histocompatibility locus antigen (HLA) class II molecules, and HLA association have been found in autoimmune skin diseases, we determined by allele-specific oligonucleotide typing whether HLA-DR or DQ alleles were associated with CTCL and its two variants MF (n = 47) and SS (n = 23). Phenotypic frequencies were compared by chi-square and Fisher exact test, and p values were corrected independently for either 12 DR or 15 DQ alleles. HLA-DR5, previously associated with MF, was significantly increased in all 70 CTCL patients (31.5%) versus controls (11%) (uncorrected p value [Pnc] = 0.000038, odds ratio [OR] = 3.9, 1.9 < OR < 8.1), in MF patients (34%) (Pnc = 0.000047, OR = 3.62, 1.9 < OR < 10), and in SS patients (26%) (Pnc = 0.03, OR = 3, 0.9 < OR < 9.3). HLA-DQB1*03 alleles (0301, 0302, and 0303) were increased in 72% of all CTCL patients versus 49% of controls (corrected p value [Pc] = 0.014, OR = 2.7, 1.4 < OR < 5.1), in SS (82%) (Pc = 0.05, OR = 4.7, 1.4 < OR < 5), and in MF (67%) (Pnc = 0.024, OR = 2.15, 1 < OR < 4.5). DQB1*0502 was strongly increased in SS patients (Pc = 0.045, OR = 7.75, 1.25 < OR < 48). Although HLA-DQB1*0603 and HLA-DR6 (1301, 1302, and 1402) were decreased in all groups, the decreases were not statistically significant. These data suggest that certain HLA-DRB and DQB1 alleles, also associated with other T-cell-mediated skin diseases, may participate in the pathogenesis of or susceptibility to CTCL.

Alleles↗
PubMed1996

Interleukin-8 is induced in skin equivalents and is highest in those derived from psoriatic fibroblasts.

Interleukin-8 (IL-8) may be important in psoriasis as it is expressed in the stratum granulosum, attracts polymorphonuclear cells, and stimulates angiogenesis and keratinocyte mitogenesis. To study intrinsic cutaneous factors in psoriasis, we constructed skin equivalents from psoriatic or adult control fibroblasts with normal foreskin keratinocytes. IL-8 levels were measured in supernatants by enzyme-linked immunosorbent assay and in skin equivalents by immunohistochemistry and in situ hybridization. IL-8 was highly induced in skin equivalents compared to cells grown alone. Epidermal stratification varied among fibroblast lines and was correlated with IL-8 levels, but lesional and nonlesional psoriatic skin equivalents from the same donor were similar. Six fibroblast lines (two psoriasis lesion and four normal) supported only monolayers, while 12 lines (seven psoriasis lesion and five normal) produced stratification. Mean IL-8 levels were significantly lower in dermal equivalents of the first group than the second (0.78 +/- 0.40 vs 3.93 +/- 2.83 ng per ml, mean +/- SD, p = 0.01, analysis of variance). Significantly more IL-8 was secreted by psoriatic than normal fibroblast skin equivalents over 14 d (p = 0.015) with greatest differences at 1 and 4 d. Psoriatic IL-8 levels peaked first and remained increased. IL-8 protein and mRNA were initially strongest in dermal fibroblasts, and at the dermal-epidermal interface. Diffuse epidermal expression was replaced by accentuation in the stratum granulosum. Psoriatic skin equivalents were thicker, had more intense IL-8 staining, and developed invagination. We hypothesize that an IL-8 paracrine loop between fibroblasts and keratinocytes may play a key role in epidermal regeneration in the skin equivalent, in normal wound healing, and in the determination of an intrinsic psoriatic wound-healing phenotype.

Adult↗
PubMed1996

Interferon-inducible protein-10 and the pathogenesis of cutaneous T-cell lymphomas.

Human interferon-g inducible protein-10 (IP-10), a small basic protein secreted by interferon (INF)-g stimulated keratinocytes, is chemotactic for normal CD4-positive lymphocytes and inhibits early normal and leukemic hemopoietic progenitor proliferation. Cutaneous T-cell lymphoma (CTCL) is an indolent CD4-positive lymphoma characterized by multiple skin relapses before visceral dissemination. We investigated the role of IP-10 in the biology of CTCL by using immunocytochemistry to define IP-10 expression in normal and CTCL skin biopsies. Using purified recombinant (r) IP-10, we generated a rabbit antiserum that recognized and neutralized rIP-10 but did not cross-react with any keratinocyte proteins or any other chemokine. Immunoperoxidase staining of normal epidermis demonstrated that IP-10 was expressed by basal but not by differentiated keratinocytes. The epidermis overlying CTCL lesions was often hyperplastic, IP-10 immunostaining was enhanced compared to normal skin, and extended to the suprabasal keratinocytes in 25 of 26 patients for a frequency of 96%; and 95% confidence interval (CI) of 80% to 100%. However, IP-10 was detectable in the dermal or epidermal lymphoid infiltrates in only three of these 26 patients (12%; 95% Cl, 2% to 39%). Skin clinically free of CTCL demonstrated normal IP-10 immunostaining. In one patient who had matching biopsies performed before and after treatment, IP-10 was initially overexpressed before treatment but was normally expressed when he achieved remission. These results suggest that IP-10 may play a role in the epidermotropism of CTCL. More work is required to determine whether IP-10 stimulates or inhibits CTCL proliferation. A better understanding of the growth controls operating in CTCL may be used to develop curative therapies for this disorder.

Adult↗
PubMed1996

Negative regulation of two hyperproliferative keratinocyte differentiation markers by a retinoic acid receptor-specific retinoid: insight into the mechanism of retinoid action in psoriasis.

Retinoids down-regulate the expression of metalloproteinases, cytokines, and other genes involved in cell proliferation and inflammation. Tazarotene (AGN 190168), a retinoic acid receptor (RAR)-specific retinoid, is effective in the treatment of psoriasis, a hyperproliferative and inflammatory skin disease. Because negative regulation of genes appears to be important in the antiproliferative and antiinflammatory action of retinoids, we studied the down-regulation of genes in skin raft cultures by this antipsoriatic retinoid. By subtraction hybridization, we found that migration inhibitory factor-related protein (MRP-8) and skin-derived anti-leukoproteinase (SKALP) are down-regulated by AGN 190168. MRP-8 and SKALP are overexpressed in psoriatic lesions as compared to the normal epidermis, and they are markers of hyperproliferative keratinocyte differentiation. We also show that MRP-8 expression is retinoid inhibitable in cultured keratinocytes induced to differentiate with 10% serum or IFN-gamma, and that MRP-8 is inhibited by RAR but not by retinoid X receptor-specific retinoids in a dose-dependent manner. Finally, MRP-8, SKALP, and the previously characterized differentiation marker, transglutaminase I, are all down-regulated in vivo in psoriatic lesions after treatment with AGN 190168 in comparison to placebo. Taken together, these data suggest that these markers may be down-regulated by tazarotene in psoriasis through direct action on keratinocyte gene expression rather than by an overall tazarotene effect on lesional therapeutic status.

Antigens, Differentiation↗
PubMed1995

Cytokine loops involving interferon-gamma and IP-10, a cytokine chemotactic for CD4+ lymphocytes: an explanation for the epidermotropism of cutaneous T-cell lymphoma?

Human interferon-gamma (IFN-gamma)-inducible protein 10 (IP-10), a C-X-C chemokine, is secreted by IFN-gamma-stimulated keratinocytes and is chemotactic for CD4+ lymphocytes. We therefore investigated its role in the epidermotropism of cutaneous T-cell lymphoma (CTCL) that is known to express IFN-gamma mRNA in the epidermis and is characterized by an indolent course with multiple relapses that remain confined to the skin for many years. By injecting purified recombinant (r) IP-10 we generated a polyclonal rabbit antiserum that specifically recognized and neutralized rIP-10. With immunoperoxidase staining, IP-10 expression was limited to the basal epidermal keratinocytes of normal skin. In biopsies of CTCL lesions the expression of IP-10 was markedly increased and it extended to the suprabasal keratinocytes in 17 of 18 patients, but it was detectable only faintly in the dermal or epidermal lymphoid infiltrates in 2 of these 18 patients. In 1 patient who had matching biopsies performed before and after treatment, IP-10 was overexpressed before treatment, but was normally expressed in the posttreatment biopsy that showed resolution of the CTCL. Increased IP-10 expression was not detected in any of 4 patients with B-cell lymphoma involving the dermis. On the basis of these findings and a review of the literature, we propose that secretion of IFN-gamma by the lymphoid infiltrate in CTCL induces the epidermal keratinocytes to secrete IP-10 that, in turn, is chemotactic for CTCL, accounting for its epidermotropism. This model may be used as a basis for future investigations of the pathogenesis of CTCL.

Adult↗
PubMed1995

Epidermal surface antigen (MS17S1) is highly conserved between mouse and human.

A mouse monoclonal antibody ECS-1 raised to human keratinocytes detects a 35-kDa epidermal surface antigen (ESA) and causes keratinocyte dissociation in vitro. ECS-1 stains skin of 16-day mouse embryo and 8- to 9-week human fetus. Mouse Esa cDNA encodes a 379-amino-acid protein that is 99.2% identical to the human, differing at only 3 amino acids. The gene (M17S1) was mapped to mouse chromosome 11, high-lighting the conserved linkage synteny existing between human chromosome 17 and mouse chromosome 11. Although the nude locus has been mapped to the same region of chromosome 11, no abnormalities in protein, mRNA, or cDNA or genomic sequences were detected in nude mice. However, both nude and control mice were found to have a second Esa mRNA transcript that conserves amino acid sequence and molecular weight. The mouse and human 5' and 3' untranslated sequences are conserved. Similar RNA folding patterns of the 5' untranslated region are predicted despite a 91-bp insertion in the mouse. These data suggest that both the function and the regulation of ESA protein are of importance and that Esa (M17S1) is not the nude locus gene.

Amino Acid Sequence↗
PubMed1995

Lymphomatoid papulosis: a T-cell dyscrasia with a propensity to transform into malignant lymphoma.

OBJECTIVE: To describe the diagnostic difficulties, response to therapy, and clinical features of lymphomatoid papulosis and the cumulative frequency of transformation to lymphoma. DESIGN: Case series. SETTING: University hospitals. METHODS: The records of 21 patients with lymphomatoid papulosis who were seen from 1986 to 1993 were retrieved from the archives of two institutions. The entry criteria for the study were lymphomatoid papulosis misdiagnosed at the time of original presentation or lymphomatoid papulosis that later developed into lymphoma. RESULTS: When lymphomatoid papulosis tissues are pathologically examined, they are frequently confused with lymphoma, melanoma, or carcinoma. Eight of the 19 patients whose condition was misdiagnosed as malignant received either chemotherapy or radiotherapy. Although lymphomatoid papulosis responded to cytotoxic chemotherapy, the remissions were transient and promptly recurred after or during treatment. However, all five cases that became malignant responded to chemotherapy and have not recurred. Five of 21 patients (24%) developed lymphoma, but the cumulative risk for transformation after 15 years was 80%. CONCLUSIONS: Lymphomatoid papulosis can only be diagnosed accurately through a careful history in which the characteristic waxing and waning of the skin lesions is identified and through proper communication between clinicians and pathologists. Patients with lymphomatoid papulosis have an increased risk for developing lymphoma that is much higher than the 15% to 20% quoted in the literature. Patients who develop lymphoma respond well to cytotoxic chemotherapy and can be cured with appropriate therapy. Internists and oncologists need to be aware of lymphomatoid papulosis and its characteristic clinical features so that this disorder is accurately diagnosed and so that unnecessary and potentially hazardous treatment is avoided.

Adolescent↗
PubMed1995

Chronic cutaneous lupus erythematosus mimicking mycosis fungoides.

Mycosis fungoides, which is characterized by a malignant infiltrate of T lymphocytes involving the epidermis, can be confused with other inflammatory skin diseases. We report the case of a patient with skin lesions containing an infiltrate of atypical lymphocytes with epidermotropism. This patient's condition was initially diagnosed as mycosis fungoides. Repeated biopsy samples had the histologic features of chronic cutaneous lupus erythematosus. The patient had a strongly positive antinuclear antibody response and the clinical lesions responded to hydroxychloroquine, however, and these findings led to an altered diagnosis. Other disorders that either clinically or histologically mimic mycosis fungoides are reviewed, and the diagnostic evaluation of patients in whom mycosis fungoides is suspected is summarized. Chronic cutaneous lupus erythematosus should be added to the list of diseases that can mimic mycosis fungoides.

Antibodies, Antinuclear↗
PubMed1995

Cutaneous T-cell lymphoma in association with silicone breast implants.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a chronic malignancy of helper T cells with the CD4 phenotype. It occurs less frequently in young women but is increasing in incidence for unknown reasons. Silicone breast implants have been associated with T-cell-mediated autoimmune reactions. OBJECTIVE: Our purpose was to suggest the hypothesis that CTCL may arise after breast implants and that different patients with CTCL may be stimulated by different antigens. METHODS: Investigators with many patients with CTCL were queried regarding the occurrence of CTCL in women after breast implants. RESULTS: Three cases of confirmed CTCL after breast implants were identified and are reported. In one patient with Sézary syndrome and CTCL, the disease went into remission after removal of implants, resolution of chronic staphylococcal infection, and initiation of photopheresis and interferon alfa therapy. Another patient had progressive disease. CONCLUSION: CTCL may occur in association with breast implants in young female patients, but causality is unknown. If CTCL is antigen driven, then it is likely to result from several different antigens in different groups of patients.

Adult↗
PubMed1995

Zidovudine for the treatment of HIV-negative patients with psoriasis: a pilot study.

BACKGROUND: Zidovudine, an inhibitor of HIV replication, has been reported to improve psoriasis in HIV-positive patients. OBJECTIVE: Our purpose was to evaluate the safety, tolerance, and effectiveness of oral zidovudine for treating psoriasis in HIV-negative patients in a small, open-label study. METHODS: Each subject received 200 mg of zidovudine every 4 hours during waking hours, for a total of 1000 mg/day. Treatment was continued for 8 weeks, at which time the patient's response to therapy was evaluated. If a response was evident, treatment was continued for an additional 8 weeks. Clinical response was correlated with histologic changes in skin lesions at 0 and 4 weeks. RESULTS: Thirty-three percent of HIV-negative patients with psoriasis showed improvement by up to 80% after 16 weeks of therapy; decreased elevation and scaling of the psoriasis plaques were the most notable changes. No complete remissions occurred. CONCLUSION: This is the first report of the use of zidovudine to treat HIV-negative patients with psoriasis. Although zidovudine was well tolerated, it may be more effective in HIV-positive patients with psoriasis.

Administration, Oral↗