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Biomedical subjects

M Duvic

Publications and source records attributed to M Duvic.

At least 109 records · Page 6Linked to original sources
PubMed1995

Vitiligo and alopecia areata in patients with human immunodeficiency virus infection.

In patients infected with human immunodeficiency virus (HIV) the development of autoimmune diseases, while not life threatening, is an interesting phenomenon that may result from immune dysfunction or from B cell infection by HIV, Epstein-Barr virus, or other unknown viruses. Vitiligo and alopecia areata are among the autoimmune diseases that have been reported in 11 patients infected with HIV. We describe a 47-year-old man who had vitiligo and alopecia areata approximately 2 years after testing positive for HIV antibodies.

Alopecia Areata↗
PubMed1995

Human immunodeficiency virus and the skin: selected controversies.

Acquired immunodeficiency syndrome was first recognized as a new disease in 1981 because of the unusual association of Kaposi's sarcoma and Pneumocystis carinii pneumonia in young men. The skin remains one of the most important clinical markers for acquired immunodeficiency syndrome, now recognized as the end stage of infection with the human immunodeficiency virus (HIV). Indeed, an urticarial viral exanthem appearing during seroconversion may allow early identification of newly infected individuals who might benefit from administration of antiviral therapy during plasma viremia. The "asymptomatic HIV infection" is often accompanied by multiple skin complaints, which commonly include xerosis, pruritus, psoriasis/seborrheic dermatitis, and pruritic papular eruptions, the cause of which remains controversial. Psoriasis and Kaposi's sarcoma lesions share features including angiogenesis, dermal dendrocytes infected with HIV, and epidermal hyperproliferation, and are manifested by mice transgenic for HIV provirus or Tat-ltr. Changes in the immune system including T-cell function, antigen response, and shifting cytokine expression as well as a propensity for autoimmune reactions must underlie the skin immunodysfunction occurring in the setting of HIV infection. One of the most unsettling controversies suggested by in vitro data is that ultraviolet light, an effective therapy for HIV-related skin disorders, may actually activate the virus.

Animals↗
PubMed1995

Werner's syndrome.

Werner's syndrome is a rare autosomal recessive disorder that affects connective tissue throughout the body. The genetic basis is not yet known, although many laboratory abnormalities have been reported. The manifestations are widespread, and many organs may prematurely undergo changes usually associated with aging. The disease generally becomes apparent around puberty, with growth arrest and thinning and graying of hair. Rapidly progressing bilateral cataracts typically occur when patients are in their 20s and 30s. A dermatologist may be consulted because of the scleroderma-like appearance of the skin, lower-extremity ulcers or calluses, thinning and graying of hair or baldness, nail dystrophy or loss, wrinkling and aging of the face, or skin cancers. Patients should have a thorough clinical and laboratory work-up, keeping in mind their elevated risk for neoplasms.

Adult↗
PubMed1994

Cloning and characterization of a novel epidermal cell surface antigen (ESA).

We report here the isolation and characterization of a cDNA that encodes a novel extracellular epidermal molecule, epidermal surface antigen (ESA), which is thought to play a role in intercellular epidermal adhesion. Sequence analysis reveals that the 379 amino acid ESA has a molecular mass of about 41.7 kDa and an alpha-helix-rich secondary conformation. Much of this also has an heptad substructure, consistent with the formation of several bundles of alpha-helices in a compact globular structure. The ESA protein appears to consist of an NH2-terminal hydrophobic region with mixed alpha and beta structure followed by a more hydrophilic COOH-terminal region which is very rich in alpha-helix. The 2.5-kilobase ESA mRNA is expressed in cultured keratinocytes, melanocytes, fibroblasts, carcinoma, and melanoma cell lines. The ESA gene is conserved in all mammalian species examined and has been localized to human chromosome 17 (M17S1) in the same region as the gene for von Recklinghausen neurofibromatosis. The high level of expression of the ESA mRNA in human skin and in cultured cells derived from the epidermis, the appearance of ESA protein early in human development, and conservation of the ESA gene throughout mammalian evolution suggest that the novel ESA protein plays a vital role in epidermal structure and maintenance.

Amino Acid Sequence↗
PubMed1994

2-Chlorodeoxyadenosine therapy in patients with T-cell lymphoproliferative disorders.

Mature T-cell lymphoproliferative disorders comprise a heterogenous group of diseases for which there is no standard therapy. These disorders are uncommon, and are usually treated similarly to their B-cell counterparts, but with less success. Nucleoside analogues have proven effective in indolent B-cell disorders but have been less well explored in T-cell malignancies. We treated 22 patients with mature T-cell lymphoproliferative diseases with 2-chlorodeoxyadenosine (2-CDA) administered as a continuous infusion at a daily dose of 4 mg/m2 over 7 days. Nineteen of the patients had received prior therapy with a median number of prior regimens of three. Eleven patients had leukemia or large granular lymphocytosis, eight patients had mycosis fungoides, and three had T-cell lymphoma. Nine patients (41%) responded to 2-CDA. Four of the patients had responses that were complete remissions, and three of these four patients remain in remission at 23, 24, and 23 months. The only important toxic effects were fever or infection, seen during 38% of courses. In conclusion, 2-CDA appears to be an effective therapy in T-cell lymphoproliferative disorders and deserves wider evaluation in this subset of patients.

Adult↗
PubMed1994

Emergence of leprosy in a patient with mycosis fungoides.

A patient with mycosis fungoides that had progressed to tumor stage responded to chemotherapy and electron beam treatment, but 6 years later a peripheral neuropathy, extensive plaques, erythroderma, and enlarged pinnae containing acid-fast organisms developed while he was being treated with photopheresis. The skin lesions cleared with administration of rifampin and dapsone, but a reversal reaction biopsy specimen showed features of both mycosis fungoides and leprosy. This case raises the question of whether there may be an association between mycosis fungoides and leprosy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Response of psoriasis to a new topical retinoid, AGN 190168.

BACKGROUND: Oral retinoids have been widely used in psoriasis, but topical forms have been ineffective or irritating. OBJECTIVE: Our purpose was to determine the clinical and molecular effects of a new topical retinoid, AGN 190168, on psoriasis. METHODS: Seven patients with psoriasis were treated for 2 weeks with topical retinoid and 2 weeks with vehicle. Two control subjects with psoriasis were treated for 2 weeks with vehicle alone. Biopsy specimens from normal skin as well as from untreated and treated psoriatic lesions were compared by immunohistochemical analysis. Differentiation and inflammatory markers were studied. RESULTS: Clinical improvement was seen in all seven patients after 2 weeks of treatment. Improvement was still present, but not significant, after 2 additional weeks of vehicle application. Histologic examination showed a return to a more normal morphology in four of seven biopsy specimens, which correlated with filaggrin expression. There was a diminution in the precocious expression of keratinocyte transglutaminase, keratin 16, and involucrin, as well as a decrease in epidermal growth factor receptor and in the number of cells expressing intercellular adhesion molecule type 1 and HLA-DR. CONCLUSION: Clinical and histologic improvements were seen in psoriasis in association with the topical application of AGN 190168 at 2 weeks, including decreased inflammation and restoration of normal epidermal differentiation. Small patient numbers and the possibility that the changes were related to clinical improvement alone and not the topical agent preclude definitive conclusions.

Administration, Cutaneous↗
PubMed1994

Localization of the gene whose mutations underlie Hailey-Hailey disease to chromosome 3q.

Hailey-Hailey disease (familial benign chronic pemphigus) is an autosomal dominant skin disease characterized by impaired keratinocyte cohesion and consequent blister formation. In the present study we have used linkage analysis to map the gene for this disease to a region of chromosome 3q between D3S1589 and D3S1316. The maximum combined two point lod score in four families studied was 14.60 at theta = 0 at the D3S1290 microsatellite repeat. These findings suggest the presence of a gene not previously known to be involved in keratinocyte cohesion at this site.

Chromosome Mapping↗
PubMed1994

Three-dimensional laser-scanning confocal microscopy of in situ hybridization in the skin.

In situ hybridization is an important tool in molecular and developmental biology to detect specific nucleic acid sequences (either mRNA or DNA) within cells. This technique is especially applicable to tissue sections since it provides information about the spatial distribution of DNA or mRNA sequences. However, previous studies utilizing in situ hybridization in the skin were hampered by a high degree of nonspecific background, which has made interpretation of the results difficult. In this paper, we demonstrate how refinements in in situ hybridization techniques, combined with laser-scanning confocal microscopy, significantly reduce nonspecific background and produce improved resolution of in situ hybridization in skin specimens. The sensitive detection method of laser-scanning confocal microscopy allows three-dimensional localization of S35 radioactive-labeled riboprobes within the emulsion of specimens, which is not possible with conventional bright or dark field light microscopy.

Dendritic Cells↗
PubMed1994

Keratinocyte transglutaminase expression varies in squamous cell carcinomas.

Type I transglutaminase (TGase I, keratinocyte or particulate transglutaminase) is a 92-kilodalton (kDa) protein expressed in abundance in cultured keratinocytes and in the hyperproliferative skin disorder psoriasis. To determine the expression of TGase I protein and mRNA, we studied tissue and established squamous carcinoma lines derived from different sources. Immunohistochemistry and Western blotting were used to detect TGase I protein with the B.C1 mouse monoclonal antibody. Only well-differentiated, skin-derived squamous carcinomas stained for TGase I. However, a precocious pattern of expression was seen overlying less-differentiated tumors. Compared to cultured human keratinocytes, squamous cell carcinoma (SCC) had many times less to 7.8 times more TGase I protein, greatest in the two most differentiated tumor lines 14-83 and ME-180. TGase I mRNA levels ranged from 0.010 to 0.00004 pg/microgram total RNA by reverse transcriptase-polymerase chain reaction using an internal standard. Protein expression correlated with mRNA levels in most SCC lines. When a human TGase I promoter was isolated and used to study genomic DNA, SCC1-83 was shown to have unique restriction enzyme fragments, including one indicative of methylation differences, also present within DNA from the KB line. These studies suggest that transcriptional control of TGase I gene expression in squamous carcinomas may be influenced both by cis elements in the promoter and by the degree of tumor squamous differentiation.

Alleles↗
PubMed1994

Epidemiology of psoriasis: clinical issues.

Psoriasis is a genetically inherited spectrum of skin diseases characterized by epidermal proliferation and inflammation, which are reversible. Although many have reported that psoriasis is triggered by trauma, infections, stress, drugs, etc., the epidemiology of psoriasis remains poorly understood. Linkage to human leukocyte antigen-(HLA)-Cw6 and DR7 is strong in people with early onset disease, but concordance in monozygotic twins is only 67%, emphasizing the importance of a triggering event. Other factors that have been reported to affect the course of psoriasis include upper respiratory infections, smoking, obesity, alcohol ingestion, regional enteritis, and human immunodeficiency virus infection. This manuscript reviews the clinical epidemiology of psoriasis and highlights some of the needs for further investigation into specific areas of the disease.

Humans↗
PubMed1994

Human leukocyte antigen-DQB1*03 alleles are associated with alopecia areata.

Alopecia areata (AA) is characterized by hair loss in patches (patchy AA), over the entire scalp (AT, totalis), or universally (AU). An autoimmune mechanism has been hypothesized, because the inflammatory infiltrate targeted to the hair follicles includes activated T cells. To investigate whether or not genetic polymorphism of the human leukocyte antigen (HLA) region contributes to disease susceptibility, we used sequence-specific oligonucleotides and amplified genomic DNA to define HLA-DQA1, -DQB1, and -DPB1 alleles in a cohort of 85 white patients. The frequency of DQB1*0301 was significantly increased to 41% in all patients, and to 47% in AT/AU patients relative to controls (27%). Analyzed together, DQB1*03 alleles (DQB1*0301-*0303) were increased to 80% (all patients) and to 92% (AT/AU) (odds ratio = 12.14, p = 0.00003, corrected). This striking association implicates the DQB1*03 alleles in the pathogenesis of AA. DQB1*06 was decreased relative to controls (56%) in all patients (32%, odds ratio = 0.37, p = 0.0045, corrected). An increase was observed in the HLA-DRB1*11(DR5) allele DRB1*1104, which may result from linkage disequilibrium with DQB1 alleles. Sequence comparison among the allele products associated with AA indicates that the DQB1*03 alleles carry a unique proline at position 55 that is not present in alleles that are neutral or negatively associated with the disease. This highly significant association may exert considerable control over immune responsiveness and the initiation or persistence of a T-cell autoimmune response against the hair follicle.

Alleles↗
PubMed1994

Zidovudine improves psoriasis in human immunodeficiency virus-positive males.

BACKGROUND AND DESIGN: Patients with human immunodeficiency virus (HIV) infection can develop severe psoriasis, which is difficult to treat using conventional therapy. Anecdotal case reports have suggested that administration of zidovudine can improve psoriasis in the HIV-infected patient. An open-label study was conducted to determine the safety and effectiveness of zidovudine therapy in 24 patients with HIV-associated psoriasis and to correlate response with laboratory and clinical variables. RESULTS: Of 19 evaluable patients, 90% had either partial (58%) or complete (32%) improvement of their HIV-associated psoriasis during zidovudine therapy. Greater than 75% reduction in the body surface area involved was positively associated with antigenemia and an age younger than 30 years. CONCLUSIONS: Zidovudine therapy, at a dosage of 1200 mg/d, appears to be beneficial in the treatment of HIV-associated psoriasis, although long-term relapses occurred and the associated arthritis did not improve.

Adult↗
PubMed1994

Severe neonatal Marfan syndrome resulting from a de novo 3-bp insertion into the fibrillin gene on chromosome 15.

Severe neonatal Marfan syndrome has features of the Marfan syndrome and congenital contractural arachnodactyly present at birth, along with unique features such as loose, redundant skin and pulmonary emphysema. Since the Marfan syndrome and congenital contractural arachnodactyly are due to mutations in different genes, it has been uncertain whether neonatal Marfan syndrome is due to mutations in the fibrillin gene on chromosome 15 or in another gene. We studied an infant with severe neonatal Marfan syndrome. Dermal fibroblasts were metabolically labeled and found to secret fibrillin inefficiently when compared with control cells. Reverse transcription and amplification of the proband's fibroblast RNA was used to identify a 3-bp insertion between nucleotides 480-481 or 481-482 of the fibrillin cDNA. The insertion maintains the reading frame of the protein and inserts a cysteine between amino acids 160 and 161 in an epidermal growth-factor-like motif of fibrillin. This 3-bp insertion was not found in the fibrillin gene in 70 unrelated, unaffected individuals and 11 unrelated individuals with the Marfan syndrome. We conclude that neonatal Marfan syndrome is the result of mutations in the fibrillin gene on chromosome 15 and is part of the Marfan syndrome spectrum.

Base Sequence↗