Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 18 de 18
Filter
Add more filters










Publication year range
1.
2.
Pediatr Dermatol ; 29(5): 629-32, 2012.
Article in English | MEDLINE | ID: mdl-22010956

ABSTRACT

A 14-year-old girl presented with a 3-week history of mucosal erosions, injected conjunctiva, dehydration, and respiratory distress. She had been treated with intravenous acyclovir for herpes simplex infection with positive herpes simplex virus immunoglobulin M and immunoglobulin G. Physical examination and imaging revealed a large abdominal mass. Incisional biopsy was obtained, and pathology demonstrated angiofollicular hyperplasia with hyalinized germinal centers and Castleman's syndrome-like features. Based on the mucosal erosions, herpes simplex virus serology and positive herpes simplex virus-1 direct fluorescent antibody, Castleman's disease secondary to overwhelming herpes simplex virus infection was the initial impression. The poor response to antivirals and subsequent development of a bullous eruption on the hands resulted in dermatology consultation. Skin biopsy was obtained from a bullae and revealed suprabasilar acantholysis with necrosis as well as upper dermal, perivascular, and interface infiltrate of lymphocytes and eosinophils. No viropathic changes were present. Direct immunofluorescence was significant for immunoglobulin G deposition intercellularly and along the dermoepidermal junction and focal trace C3 deposition along the dermoepidermal junction consistent with paraneoplastic pemphigus, later confirmed by indirect immunofluorescence. We report this case of paraneoplastic pemphigus secondary to Castleman's syndrome confounded by herpes simplex virus-1 positive mucosal erosions.


Subject(s)
Castleman Disease/virology , Herpes Simplex/diagnosis , Paraneoplastic Syndromes/virology , Pemphigus/virology , Acantholysis/drug therapy , Acantholysis/immunology , Acantholysis/pathology , Acantholysis/virology , Acyclovir/therapeutic use , Adolescent , Antiviral Agents/therapeutic use , Biopsy , Castleman Disease/drug therapy , Castleman Disease/immunology , Castleman Disease/pathology , Complement C3/analysis , Complement C3/immunology , Eosinophils/immunology , Female , Fluorescent Antibody Technique , Herpes Simplex/drug therapy , Herpes Simplex/immunology , Herpes Simplex/pathology , Humans , Immunoglobulin M/analysis , Immunoglobulin M/immunology , Lymphocytes/immunology , Paraneoplastic Syndromes/drug therapy , Paraneoplastic Syndromes/immunology , Paraneoplastic Syndromes/pathology , Pemphigus/drug therapy , Pemphigus/immunology , Pemphigus/pathology , Treatment Outcome
4.
Obstet Gynecol Surv ; 65(7): 455-61, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20723267

ABSTRACT

UNLABELLED: Paraneoplastic dermatoses are a heterogeneous group of skin disorders that manifest an underlying internal malignancy. Early recognition of these cutaneous hallmarks offers an opportunity for early diagnosis, treatment of the internal malignancy and monitoring for tumor recurrence. The 9 most common paraneoplastic and metastatic cutaneous manifestations of malignancies found in women with gynecologic or breast disease are reviewed including a review of multicentric reticulohistiocytosis, dermatomyositis, malignant acanthosis nigricans, erythema gyratum repens, hypertrichosis lanuginosa acquisita, Sweet syndrome, Paget disease, extramammary Paget disease, and Sister Mary Joseph nodule. TARGET AUDIENCE: General obstetricians & gynecologists, reproductive endocrinology & infertility specialists, radiologists. LEARNING OBJECTIVES: After completion of this educational activity, the participant should be better able to identify cutaneous manifestations of gynecologic malignancies, evaluate patients with a thorough workup to screen those who have dermatoses suggestive of malignancy and assess patients with malignancy for the opportunity of early diagnosis and appropriate treatment.


Subject(s)
Breast Neoplasms/complications , Dermatomyositis/etiology , Genital Neoplasms, Female/complications , Paraneoplastic Syndromes/etiology , Skin Diseases/etiology , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Dermatomyositis/pathology , Female , Genital Neoplasms, Female/diagnosis , Genital Neoplasms, Female/pathology , Humans , Paraneoplastic Syndromes/pathology , Skin Diseases/pathology
5.
J Cutan Pathol ; 37(10): 1038-40, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20412344

ABSTRACT

Onychomycosis is a frequently treated fungal infection of the nail plate with morbidity in high-risk populations. The diagnosis often relies on histopathologic analysis of nail plate specimens with the assistance of special stains. Pathologists utilize periodic acid schiff (PAS) and/or Gomori methenamine silver (GMS) stains to highlight fungi within the nail plate. In a recent study of 51 PAS-negative nail cases, it was concluded that GMS is superior to PAS in the diagnosis of onychomycosis. We expand on this study by investigating a larger number of PAS-negative nail clippings determining whether GMS or PAS is superior in highlighting fungi in additional sections. There was no difference in the sensitivity of PAS vs. GMS (4.2 vs. 4.3%, p = 0.57); however, PAS was found to be significantly less expensive by 2.6-fold. Taken together, these data suggest that the PAS stain is the optimal method for diagnosing onychomycosis.


Subject(s)
Foot Dermatoses/diagnosis , Hand Dermatoses/diagnosis , Onychomycosis/diagnosis , Periodic Acid-Schiff Reaction , Humans , Periodic Acid-Schiff Reaction/economics , Sensitivity and Specificity , Silver Staining/economics
6.
J Dermatolog Treat ; 19(6): 318-26, 2008.
Article in English | MEDLINE | ID: mdl-18626814

ABSTRACT

Th17 cells, named for their secretion of interleukin-17 (IL-17), are a new class of T-cells involved in a wide range of cutaneous autoimmune and inflammatory conditions. An overactive Th17 cell response in the skin can produce damaging results. There appears to be a partial role for the Th17 axis in the pathogenesis of a range of dermatological diseases including allergic contact dermatitis, atopic dermatitis, psoriasis, and scleroderma. Immunologists have also discovered a unique association between Th17 cells and cutaneous T-cell lymphoma. The Th17 branch has been linked to a number of additional systemic inflammatory diseases with significant cutaneous pathology such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and Behcet's disease. Newly developed treatment modalities for neutralizing the Th17 branch of the immune system are proving to be valuable additions to the current therapeutic armamentarium.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Immunologic Factors/therapeutic use , Interleukin-17/immunology , Skin Diseases/drug therapy , Skin Diseases/immunology , Antibodies, Monoclonal, Humanized , Biomarkers/metabolism , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/immunology , Drug Therapy, Combination , Humans , Injections, Subcutaneous , Interleukin-17/genetics , Interleukin-23/genetics , Interleukin-23/immunology , Interleukins/genetics , Interleukins/immunology , Polymorphism, Genetic , Psoriasis/drug therapy , Psoriasis/immunology , Randomized Controlled Trials as Topic , Scleroderma, Systemic/drug therapy , Scleroderma, Systemic/immunology , Skin Diseases/genetics , Treatment Outcome , Ustekinumab , Interleukin-22
7.
J Dermatolog Treat ; 19(5): 259-66, 2008.
Article in English | MEDLINE | ID: mdl-18629676

ABSTRACT

Inflammatory processes of the skin have classically been segregated to either the cell-mediated, T-helper type 1 (Th1) or the humoral (Th2) branch of the immune system. The recent addition of Th17 cells, a novel T-helper cell named for its secretion of interleukin (IL)-17, to current thinking in autoimmunity has resulted in a significant paradigm shift in immunological thinking. Collectively, Th17 cytokines have been found to stimulate cutaneous immune reactions through an activation of a wide range of downstream inflammatory mediators and an induction of immune cell and keratinocyte proliferation as well as angiogenesis. Newly developed treatment modalities for neutralizing the Th17 branch of the immune system are proving to be valuable additions to the current therapeutic armamentarium. Here we describe a new schema for dermatologic T-cell-mediated immunity. We elucidate experiments confirming the presence of Th17 cells, followed by a discussion of their relevance to cutaneous inflammation and psoriasis.


Subject(s)
Dermatitis/immunology , Dermatitis/pathology , Interleukin-17/physiology , T-Lymphocytes, Helper-Inducer/physiology , Animals , Humans
9.
Pediatr Dermatol ; 23(5): 497-9, 2006.
Article in English | MEDLINE | ID: mdl-17014651

ABSTRACT

We report three teenaged Caucasian patients with confluent and reticulated papillomatosis whose presentation was atypical due to the absence of hyperpigmentation and presence of a fine white scale.


Subject(s)
Papilloma/pathology , Skin Neoplasms/pathology , Adolescent , Adult , Female , Humans , Male
10.
Adv Dermatol ; 21: 357-74, 2005.
Article in English | MEDLINE | ID: mdl-16350450

ABSTRACT

The ability of the cutaneous barrier to help defend the body against pathogens relies on both acquired and innate immune responses. Recently, a large body of research has suggested that a critical component of the innate immune response in the skin is 3 antimicrobial peptides: the cathelicidins, defensins, and dermcidins. These 3 classes of peptides have been shown to act as antimicrobials by directly inhibiting pathogen growth as well as potentiating other branches of the innate, humoral, and cell-mediated immune system. Here, we review the antimicrobial peptides with an emphasis on their role in the cutaneous immune response. We present an overview of defensin, cathelicidin, and dermcidin physiology, elucidating their various functions. In addition, we delve into the role of these peptides in specific dermatologic conditions including wound healing, atopy, and microbial infection. Finally, we discuss the future of antimicrobial peptide research including therapeutic options.


Subject(s)
Antimicrobial Cationic Peptides/immunology , Defensins/immunology , Peptides/immunology , Skin/immunology , Antimicrobial Cationic Peptides/metabolism , Antimicrobial Cationic Peptides/physiology , Defensins/metabolism , Defensins/physiology , Humans , Immunity, Innate , Peptides/metabolism , Peptides/physiology , Skin/microbiology , Skin Diseases/immunology , Skin Diseases/metabolism , Cathelicidins
11.
Hum Mol Genet ; 14(4): 513-24, 2005 Feb 15.
Article in English | MEDLINE | ID: mdl-15640247

ABSTRACT

Chromatin remodeling complexes play critical roles in development. Here we describe a transcription factor, CECR2, which is involved in neurulation and chromatin remodeling. CECR2 shows complex alternative splicing, but all variants contain DDT and bromodomain motifs. A mutant mouse line was generated from an embryonic stem cell line containing a genetrap within Cecr2. Reporter gene expression demonstrated Cecr2 expression to be predominantly neural in the embryo. Mice homozygous for the Cecr2 genetrap-induced mutation show a high penetrance of the neural tube defect exencephaly, the human equivalent of anencephaly, in a strain-dependent fashion. Biochemical isolation of CECR2 revealed the presence of this protein as a component of a novel heterodimeric complex termed CECR2-containing remodeling factor (CERF). CERF comprises CECR2 and the ATP-dependent chromatin remodeler SNF2L, a mammalian ISWI ortholog expressed predominantly in the central nervous system. CERF is capable of remodeling chromatin in vitro and displays an ATP hydrolyzing activity that is stimulated by nucleosomes. Together, these data identify a novel chromatin remodeling complex with a critical role in neurulation.


Subject(s)
Central Nervous System/embryology , Chromatin Assembly and Disassembly , Chromatin , DNA-Binding Proteins/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Transcription Factors/metabolism , Adenosine Triphosphatases/metabolism , Adenosine Triphosphate/metabolism , Alternative Splicing , Animals , Cells, Cultured , Central Nervous System/metabolism , DNA-Binding Proteins/genetics , Female , Intercellular Signaling Peptides and Proteins/genetics , Male , Mice , Mice, Inbred BALB C , Mutation , Neural Tube Defects , Nucleosomes/metabolism , Transcription Factors/genetics
12.
J Biol Chem ; 279(43): 45130-8, 2004 Oct 22.
Article in English | MEDLINE | ID: mdl-15310751

ABSTRACT

Mammalian genomes encode two imitation switch family chromatin remodeling proteins, SNF2H and SNF2L. In the mouse, SNF2H is expressed ubiquitously, whereas SNF2L expression is limited to the brain and gonadal tissue. This pattern of SNF2L expression suggests a critical role for SNF2L in neuronal physiology. Indeed, SNF2L was shown to promote neurite outgrowth as well as regulate the human engrailed homeotic genes, important regulators of brain development. Here we identify a novel splice variant of human SNF2L we call SNF2L+13, which contains a nonconserved in-frame exon within the conserved catalytic core domain of SNF2L. SNF2L+13 retains the ability to incorporate into multiprotein complexes; however, it is devoid of enzymatic activity. Most interestingly, unlike mouse SNF2L, human SNF2L is expressed ubiquitously, and regulation is mediated by isoform variation. The human SNF2L+13 null variant is predominant in non-neuronal tissue, whereas the human wild type active SNF2L isoform is expressed in neurons. Thus, like the mouse, active human SNF2L is limited to neurons and a few other tissues.


Subject(s)
DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Transcription Factors/biosynthesis , Transcription Factors/genetics , Adenosine Triphosphatases/chemistry , Alternative Splicing , Amino Acid Sequence , Animals , Brain/metabolism , Catalytic Domain , Cell Line , Cell Nucleus/metabolism , Chromatin/chemistry , Chromatin/metabolism , Chromatography , DNA Restriction Enzymes/pharmacology , Dose-Response Relationship, Drug , Electrophoresis, Polyacrylamide Gel , Exons , HeLa Cells , Humans , Immunoblotting , Immunoprecipitation , Mice , Models, Biological , Models, Genetic , Molecular Sequence Data , Neurons/metabolism , Polymerase Chain Reaction , Protein Folding , Protein Isoforms , Protein Structure, Tertiary , RNA, Messenger/metabolism , Recombinant Proteins/chemistry , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Amino Acid , Transfection
13.
J Biol Chem ; 279(19): 20369-77, 2004 May 07.
Article in English | MEDLINE | ID: mdl-14990586

ABSTRACT

Death domain-associated protein (Daxx) is a multi-functional protein that modulates both apoptosis and transcription. Within the nucleus, Daxx is a component of the promyelocytic leukemia protein (PML) nuclear bodies (NBs) and interacts with a number of transcription factors, yet its precise role in transcription remains elusive. To further define the function of Daxx, we have isolated its interacting proteins in the nucleus using epitope-tagged affinity purification and identified X-linked mental retardation and alpha-thalassaemia syndrome protein (ATRX), a putative member of the SNF2 family of ATP-dependent chromatin remodeling proteins that is mutated in several X-linked mental retardation disorders. We show that substantial amounts of endogenous Daxx and ATRX exist in a nuclear complex. Daxx binds to ATRX through its paired amphipathic alpha helices domains. ATRX has ATPase activity that is stimulated by mononucleosomes, and patient mutations in the ATPase domain attenuate this activity. ATRX strongly represses transcription when tethered to a promoter. Daxx does not affect the ATPase activity of ATRX, however, it alleviates its transcription repression activity. In addition, ATRX is found in the PML-NBs, and this localization is mediated by Daxx. These results show that the ATRX.Daxx complex is a novel ATP-dependent chromatin-remodeling complex, with ATRX being the core ATPase subunit and Daxx being the targeting subunit. Moreover, the localization of ATRX to the PML-NBs supports the notion that these structures may play an important role in transcription regulation.


Subject(s)
Carrier Proteins/physiology , DNA Helicases , DNA-Binding Proteins/physiology , Intracellular Signaling Peptides and Proteins , Nuclear Proteins/physiology , Transcription Factors/physiology , Transcription, Genetic , Adaptor Proteins, Signal Transducing , Adenosine Triphosphatases/chemistry , Adenosine Triphosphate/chemistry , Amino Acid Sequence , Carrier Proteins/chemistry , Cell Line , Cell Nucleus/metabolism , Chromatin/metabolism , Chromatography, Gel , Co-Repressor Proteins , DNA/chemistry , DNA-Binding Proteins/chemistry , Dose-Response Relationship, Drug , Epitopes/chemistry , Gene Deletion , Gene Expression Regulation , Genes, Reporter , HeLa Cells , Humans , Microscopy, Fluorescence , Models, Biological , Molecular Chaperones , Molecular Sequence Data , Mutation , Nuclear Proteins/chemistry , Plasmids/metabolism , Precipitin Tests , Protein Binding , Protein Structure, Secondary , Protein Structure, Tertiary , Recombinant Proteins/chemistry , Transcription Factors/chemistry , X-linked Nuclear Protein
15.
EMBO J ; 22(22): 6089-100, 2003 Nov 17.
Article in English | MEDLINE | ID: mdl-14609955

ABSTRACT

The modification of chromatin structure is an important regulatory mechanism for developmental gene expression. Differential expression of the mammalian ISWI genes, SNF2H and SNF2L, has suggested that they possess distinct developmental roles. Here we describe the purification and characterization of the first human SNF2L-containing complex. The subunit composition suggests that it represents the human ortholog of the Drosophila nucleosome-remodeling factor (NURF) complex. Human NURF (hNURF) is enriched in brain, and we demonstrate that it regulates human Engrailed, a homeodomain protein that regulates neuronal development in the mid-hindbrain. Furthermore, we show that hNURF potentiates neurite outgrowth in cell culture. Taken together, our data suggess a role for an ISWI complex in neuronal growth.


Subject(s)
DNA-Binding Proteins/metabolism , Homeodomain Proteins/genetics , Nuclear Proteins , Nucleosomes/metabolism , Transcription Factors/metabolism , Adenosine Triphosphatases/isolation & purification , Adenosine Triphosphatases/metabolism , Animals , Antigens, Nuclear , Cerebellum/metabolism , DNA Helicases , DNA-Binding Proteins/isolation & purification , Gene Expression Regulation, Developmental , Hippocampus/metabolism , Homeodomain Proteins/biosynthesis , Humans , Mice , Nerve Tissue Proteins/metabolism , Neurites/metabolism , Promoter Regions, Genetic , Transcription Factors/isolation & purification
16.
Nature ; 418(6901): 994-8, 2002 Aug 29.
Article in English | MEDLINE | ID: mdl-12198550

ABSTRACT

Nucleosomal DNA is arranged in a higher-order structure that presents a barrier to most cellular processes involving protein DNA interactions. The cellular machinery involved in sister chromatid cohesion, the cohesin complex, also requires access to the nucleosomal DNA to perform its function in chromosome segregation. The machineries that provide this accessibility are termed chromatin remodelling factors. Here, we report the isolation of a human ISWI (SNF2h)-containing chromatin remodelling complex that encompasses components of the cohesin and NuRD complexes. We show that the hRAD21 subunit of the cohesin complex directly interacts with the ATPase subunit SNF2h. Mapping of hRAD21, SNF2h and Mi2 binding sites by chromatin immunoprecipitation experiments reveals the specific association of these three proteins with human DNA elements containing Alu sequences. We find a correlation between modification of histone tails and association of the SNF2h/cohesin complex with chromatin. Moreover, we show that the association of the cohesin complex with chromatin can be regulated by the state of DNA methylation. Finally, we present evidence pointing to a role for the ATPase activity of SNF2h in the loading of hRAD21 on chromatin.


Subject(s)
Adenosine Triphosphatases/metabolism , Cell Cycle Proteins/metabolism , Chromatin/chemistry , Chromatin/metabolism , Chromosomal Proteins, Non-Histone/metabolism , Chromosomes, Human/chemistry , Chromosomes, Human/metabolism , Nuclear Proteins/metabolism , Phosphoproteins/metabolism , Alu Elements/genetics , Chromatin/genetics , Chromosomes, Human/genetics , DNA/chemistry , DNA/genetics , DNA/metabolism , DNA Methylation , DNA-Binding Proteins/metabolism , Fungal Proteins , HeLa Cells , Humans , Macromolecular Substances , Precipitin Tests , Protein Binding , Protein Subunits , Retroelements/genetics , Cohesins
17.
Genomics ; 79(4): 523-9, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11944984

ABSTRACT

The PHD/LAP (plant homology domain/leukemia associated protein) finger motif is characteristically defined by a histidine and seven cysteines that are spatially arranged in a C4HC3 consensus sequence. This unique zinc finger, found primarily in a wide variety of chromatin-associated proteins, is considered to mediate protein-protein interactions. We have isolated a novel human PHD-finger protein, HBXAP (for hepatitis B virus x associated protein). HBXAP has three alternatively spliced isoforms. We also identified the Drosophila melanogaster HBXAP ortholog, gene CG8677. Based on alignment of four different proteins, we found a novel conserved domain in HBXAP that we designated the HBXAP conserved domain (XCD). We show that HBXAP represses transcription when recruited to DNA via the DNA binding of GAL4. Furthermore, the PHD finger alone suffices to repress transcription, thus attributing a functional role to this domain. The gene HBXAP is localized to the long arm of human chromosome 11 between q13.4 and q14.1. This region is amplified and rearranged in many tumors, suggesting a role for HBXAP in tumorigenesis similar to that of other PHD-containing proteins.


Subject(s)
Chromosomes, Human, Pair 11 , Genome, Human , Nuclear Proteins/genetics , Trans-Activators/genetics , Transcription, Genetic , Amino Acid Motifs/genetics , Amino Acid Sequence , Chromosome Mapping , Down-Regulation , Humans , Molecular Sequence Data , Protein Isoforms/genetics , Sequence Alignment , Sequence Homology
18.
J Biol Chem ; 277(12): 9982-8, 2002 Mar 22.
Article in English | MEDLINE | ID: mdl-11788598

ABSTRACT

Hepatitis B virus (HBV) gene expression is mainly regulated at the transcription initiation level. The viral X protein (pX) is a transcription coactivator/mediator targeting TFIIB for the recruitment of RNA polymerase II. Here we report a novel pX nuclear target designated HBXAP (hepatitis B virus X-associated protein). HBXAP is a novel cellular nuclear protein containing a PHD (plant homology domain) finger, a domain shared by many proteins that play roles in chromatin remodeling, transcription coactivation, and oncogenesis. pX physically interacts with HBXAP in vitro and in vivo via the HBXAP region containing the PHD finger. At the functional level HBXAP increases HBV transcription in a pX-dependent manner suggesting a role for this interaction in the virus life cycle. Interestingly, HBXAP collaborates with pX in coactivating the transcriptional activator NF-kappaB. Coactivation of NF-kappaB was also observed in tumor necrosis factor alpha-treated cells suggesting that pX-HBXAP functional collaboration localized downstream to the NF-kappaB nuclear import. Collectively our data suggest that pX recruits and potentiates a novel putative transcription coactivator to regulate NF-kappaB. The implication of pX-HBXAP interaction in the development of hepatocellular carcinoma is discussed.


Subject(s)
Hepatitis B virus/metabolism , Nuclear Proteins/metabolism , Trans-Activators/metabolism , Transcriptional Activation , Viral Regulatory and Accessory Proteins/metabolism , Amino Acid Motifs , Amino Acid Sequence , Animals , Blotting, Western , COS Cells , Carcinoma, Hepatocellular/metabolism , Cell Line , Cell Nucleus/metabolism , DNA, Complementary/metabolism , Escherichia coli/metabolism , Genetic Complementation Test , Humans , Liver Neoplasms/metabolism , Molecular Sequence Data , NF-kappa B/metabolism , Nuclear Proteins/chemistry , Nuclear Proteins/genetics , Plasmids/metabolism , Precipitin Tests , Protein Binding , Protein Structure, Tertiary , RNA/metabolism , Sequence Homology, Amino Acid , Temperature , Trans-Activators/chemistry , Trans-Activators/genetics , Transfection , Tumor Cells, Cultured , Tumor Necrosis Factor-alpha/metabolism , Two-Hybrid System Techniques
SELECTION OF CITATIONS
SEARCH DETAIL
...