In pemphigus foliaceus (PF), immunoglobulin G (IgG) autoantibodies directed against desmoglein-1 (Dsg-1), a cell adhesion molecule expressed mainly in the granular layer of the epidermis, are responsible for the intercellular widening between desmosomes resulting in intraepidermal blisters. Rituximab is a chimeric monoclonal antibody that by binding specifically to the transmembrane antigen CD20 found on the surface of normal and malignant B cells, leads to B-cell depletion. We report a 19-year-old Filipino woman with PF and controlled idiopathic thrombocytopenia purpura, initially treated with high-dose prednisone and azathioprine. Due to rapid PF progression with associated moderate reactive depression, rituximab was added to the treatment regimen with prompt improvement of lesions and clearance after five months. Five years later, lesions recurred with erythematous, dry, scaly plaques on both breasts, axillae, and on the scalp, associated with moderate to severe intermittent pruritus. After the first of a series of four weekly infusions, rituximab monotherapy resulted in immediate and sustained clearance up to 22 months. In parallel with skin clearance, serum CD19 and CD20 B cells decreased to almost zero after the first infusion, to zero after the second, while the decrease of Dsg-1 levels was more gradual, and down to normal after four months.
We offer this case report to show that rituximab can be given as a first-line monotherapy option for indications similar to ours such as drug reactions (steroid-induced depression) or a history of recalcitrant PF to the usual medications; and to suggest using CD19 and CD20 in addition to the desmoglein levels to monitor disease activity and molecular change from which to learn how to continue to monitor for disease activity after clearance.

Human ; Female ; Adult ; Antigens, Cd20 ; Autoantibodies ; Azathioprine ; B-lymphocytes ; Blister ; Desmosomes ; Immunoglobulin G ; Pemphigus ; Rituximab

BACKGROUND/AIMS: To establish an animal model of laryngopharyngeal reflux (LPR) and study the effect of LPR on the laryngopharyngeal mucosal ultrastructure. METHODS: Ten Bama minipigs were randomly divided into control group and stent group. Every pig underwent endoscope, and baseline pH was monitored for 4 hours at laryngopharynx and distal esophagus, then specimens from laryngopharyngeal mucosa were biopsied. For the control group, these procedures were repeated on the 14th day. In the stent group, a custom-designed esophageal stent suit was implanted into esophagus, laryngopharyngeal and distal esophageal pH monitoring lasted for 2 hours, then stent suit was removed 3 days later. At last, the same procedures were done as the control group on the 14th day. Specimens were observed under transmission electron microscope to measure the intercellular space and desmosome number. RESULTS: In the control group, there was no laryngopharyngeal reflux on the first day and 14th day. Before the stent was implanted, there was also no laryngopharyngeal reflux in the stent group. In both 2 hours and 14 days after stent implantation, the num -ber of reflux, reflux time, and percentage time of pH < 4.0 were significantly increased (P < 0.05) in the stent group. There was no difference in intercellular space and desmosomes in the control group between baseline and 14th day. In the stent group, intercellular space of laryngopharyngeal mucosa was significantly increased (0.37 mum vs 0.96 mum, P = 0.008), and the number of desmosomes was significantly decreased (20.25 vs 9.5, P = 0.003). CONCLUSIONS: A Bama minipig model of LPR was established by implanting a custom-designed stent suit. LPR might destroy the laryngophar yngeal mucosal barrier.
Desmosomes ; Endoscopes ; Esophageal pH Monitoring ; Esophagus ; Extracellular Space ; Hydrogen-Ion Concentration ; Hypopharynx ; Laryngopharyngeal Reflux* ; Models, Animal ; Mucous Membrane ; Stents ; Swine, Miniature*

The intercalated disc (ICD) complex of cardiomyocyte consists of fascia adherens, desmosomes and gap junctions which are mainly constructed by their transmembrane proteins: N-cadherin (N-cad), desmoglein-2 (DSG2) and connexin 43 (Cx43), respectively. The aim of this study was to observe the dynamic changes in colocalization of N-cad, DSG2 and Cx43 with each other in the rat left ventricular myocardium at 1, 7, 14, 28 and 90 day(s) after birth (P1, P7, P14, P28 and P90) using immunofluorescent staining. The results showed that, N-cad, DSG2 and Cx43 located all around the plasma membrane at the P1. These proteins accumulated to the long ends of cardiomyocytes, indicating preliminary formation of the ICD at the P7. The localization of three proteins at the ICD increased progressively, but their lateral localization showed an inverse trend from the P14 to P90. However, Cx43 still kept a certain amount of lateral localization in cardiomyocytes even at the P90 as compared with N-cad and DSG2. Quantitative colocalization of proteins was analyzed by the stereological method. Total percentage of colocalization of N-cad with DSG2 was 33.5% at the P1, and increased to 38.6% at the P7, 9.4% in ICD and 29.2% in lateral side. The total percentage of colocalization of N-cad with DSG2 increased to 65.7% at the P90, ICD colocalization increasing to 60.5% and lateral colocalization decreasing to 5.2%. Total percentage of colocalization of N-cad with Cx43 increased from 10.3% at the P1 to 37.1% at the P90, and only ICD colocalization increased, but lateral colocalization kept about 5%. The colocalization pattern of DSG2 with Cx43 was similar to that of N-cad with Cx43. Total percentage of colocalization of N-cad with DSG2 was higher than those of N-cad or DSG2 with Cx43. The above results suggest that the formation of mechanical junctions at the ICD of cardiomyocyte is prior to that of electrochemistry junctions during postnatal development. In other words, cardiomyocyte growth needs a stable mechanical environment at first.
Adherens Junctions ; metabolism ; Animals ; Cadherins ; metabolism ; Cell Membrane ; metabolism ; Connexin 43 ; metabolism ; Desmoglein 2 ; metabolism ; Desmosomes ; metabolism ; Gap Junctions ; metabolism ; Heart ; growth & development ; Heart Ventricles ; metabolism ; Myocytes, Cardiac ; metabolism ; Rats

Soft tissue myoepithelioma is a rare neoplasm composed of myoepithelial cells. Here, we describe the cytologic features of soft tissue myoepithelioma arising on the right forearm in an 18-year-old man. The excised tumor (3.0x1.8x1.5 cm) was well-demarcated, yellow-gray, soft, and myxoid. The cytologic smears showed round to spindle, epithelioid, and plasmacytoid cells in the myxoid background. The nuclei were uniform, round to ovoid, with finely distributed chromatin and eosinophilic or pale cytoplasm. The tumor cells demonstrated immunoreactivity for cytokeratin (AE1/AE3), epithelial membrane antigen, S100 protein, and glial fibrillary acidic protein. Electron microscopy showed intermediate filaments, desmosomes, and basal lamina.
Basement Membrane ; Chromatin ; Cytoplasm ; Desmosomes ; Eosinophils ; Forearm ; Glial Fibrillary Acidic Protein ; Intermediate Filaments ; Keratins ; Microscopy, Electron ; Mucin-1 ; Myoepithelioma

BACKGROUND: Desmocollins (Dsc) are calcium-dependent transmembrane glycoproteins of desmosomes that are important in the junction complex of epidermis and maintain structural integrity of the skin from external stressors. Among three Dscs (Dsc 1, 2, 3), Dsc 1 and 3 are distributed on skin. OBJECTIVE: The purpose of this study was to observe the Dsc 1 distribution pattern on the skin and oral mucosa during fetal development. METHODS: Skin was obtained from the sole and scalp of 33 fetuses, ranging from 10 to 37 weeks of gestational age. Immunohistochemical staining was performed on the paraffin-embedded tissue using a Dsc 1 monoclonal antibody. RESULTS: Dsc 1 was expressed in the suprabasal layer but not in the basal layer of the epidermis of the sole at the 10th week of gestation. Thereafter, Dsc 1 expression further increased in the suprabasal layer with initiation of stratification and increased gradually in the granular layers of the sole and scalp epidermis. Dsc 1 was strongly expressed in the superficial layer of the infundibulum and inner root sheath of the hair follicle but was not expressed in the sebaceous cells or other hair components. The eccrine duct epithelium was focally and weakly positive for Dsc 1 expression. Furthermore, Dsc 1 was not expressed in oral mucosa, although the oro-cutaneous portion was strongly expressed in the superficial layer. CONCLUSION: Dsc 1 was strongly expressed in the suprabasal cells of the epidermis during fetal skin development, and expression increased gradually in the granular layer and inner root sheath of the hair follicle. However, Dsc 1 was not expressed in basal cells or in oral mucosa. Dsc 1 may play a role in the maintenance of epithelial integrity as part of desmosomes.
Desmocollins ; Desmosomes ; Epidermis ; Epithelium ; Fetus ; Gestational Age ; Glycoproteins ; Hair ; Hair Follicle ; Mouth Mucosa ; Pregnancy ; Scalp ; Skin

BACKGROUND: Desmosomes are cell-cell adhesion complexes that provide mechanical integrity to keratinocytes by linking them to keratin intermediate filaments. Desmosomes are composed of two major transmembrane proteins, desmoglein and desmocollin. In humans, four desmoglein isoforms have been identified: Dsg1, Dsg2, Dsg3, and Dsg4. Desmogleins are Ca2+-dependent adhesion molecules and play important parts in the formation and maintenance of desmosomes. Desmoglein-1 is the main skin-associated desmosomal cadherin. It is expressed throughout the epidermis, but most prominently in the differentiated layers. OBJECTIVE: The purpose of this study was to observe the distribution pattern of desmoglein-1 in the skin and oral mucosa during fetal development. METHODS: Skin was obtained from the sole and scalp of 35 fetuses, ranging from 10 to 37 weeks of gestational age. Immunohistochemical staining was performed on paraffin embedded tissue using anti-human monoclonal antibody against desmoglein-1. RESULTS: Expression of desmoglein-1 in the epidermis appeared in the upper layer of the sole, but the basal layer was negative at the 10th gestational age. Thereafter, stratification began with stronger expression in the middle layer than in the basal layer of the sole and scalp epidermis. Expression in the middle spinous layer is stronger in the fetal period than in other layers of the epidermis. Expression in the superficial layer seemed to increase in later stages. Expression of desmoglein-1 in hair was strong in the infundibulum, inner root sheath, sebaceous glandular epithelium, and eccrine duct epithelium. Expression of desmoglein-1 in oral lip mucosa was very weak or negative in the upper half of the mucosal epithelium, though the lower half was strongly positive, while the skin side of the mucosa was similar with the sole skin. CONCLUSION: Desmoglein-1 may play a complementary role in the maintenance of epithelial integrity along with other desmogleins, because desmoglein-1 distribution is slightly different from that of desmoglein-3 in epidermis, hair and mucosa in fetal skin development.
Desmogleins ; Desmosomes ; Epidermis ; Epithelium ; Fetus ; Gestational Age ; Hair ; Humans ; Intermediate Filaments ; Keratinocytes ; Keratins ; Lip ; Mouth Mucosa ; Mucous Membrane ; Paraffin ; Protein Isoforms ; Proteins ; Scalp ; Skin

AIMTo investigate the role of the Chinese herbal medicine Xianhuayin on the reversal of 7,12-dimethylbenz[a]anthracene (DMBA)-induced premalignant mucosal lesions in the oral buccal pouch of golden hamsters.

METHODOLOGYThe animals were randomly divided into a non-diseased control group (n=5) and an experimental group including 50 animals in which the buccal mucosa had been painted with DMBA (0.5% in acetone) to generate an oral mucosa premalignant lesion. Animals in the experimental group were further divided into Xianhuayin-treated group (n=30), untreated premalignant lesion group (n=10) and normal saline (NS)-treated group (n=10). The cheek (buccal) pouch mucosa of the golden hamsters in each group was observed with light and electron microscopy eight weeks after intragastric administration with NS or Xianhuayin.

RESULTSIn the non-diseased control group, the buccal mucosa was keratinized and stratified squamous epithelium under a light microscope. In the untreated premalignant lesion group, variable degrees of epithelial dysplasia was observed. The irregular epithelial mucosa gradually became distinct in the Xianhuayin-treated group. Scanning electronic microscopic (SEM) analysis showed that surface of the cells exhibited honeycomb structures in the hamster of untreated-group. The cells were morphologically irregular, overlapped and loosened in the untreated premalignant lesion group. Most of the cell surface exhibited honeycomb structure in the Xianhuayin-treated group. Transmission electronic microscopic (TEM) analysis showed that buccal mucosal epithelial cells were morphologically regular in the non-diseased control group. Desmosomes and tonofibrils were reduced and the nucleus was morphologically irregular in the untreated premalignant lesion group. In the Xianhuayin-treated group, the widening intercellular gap was gradually reduced, desmosomes and the cells becoming morphologically regular. No significant difference was observed between the hamsters in NS-treated group and those in the untreated premalignant lesion group. Significant therapeutic efficacy was observed in the group receiving Xianhuayin.

CONCLUSIONXianhuayin is effective in the reversal of DMBA-induced premalignant lesions in the buccal pouch of golden hamsters.

9,10-Dimethyl-1,2-benzanthracene ; adverse effects ; Amomum ; Animals ; Anticarcinogenic Agents ; administration & dosage ; therapeutic use ; Carcinogens ; Carthamus tinctorius ; Cell Nucleus ; drug effects ; Cricetinae ; Desmosomes ; drug effects ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Epithelial Cells ; drug effects ; Epithelium ; drug effects ; Glycyrrhiza ; Hyperplasia ; Intercellular Junctions ; drug effects ; Intermediate Filaments ; drug effects ; Keratins ; Mesocricetus ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Mouth Mucosa ; drug effects ; pathology ; Mouth Neoplasms ; prevention & control ; Philodendron ; Poria ; Precancerous Conditions ; prevention & control ; Random Allocation ; Sodium Chloride

BACKGROUND: Desmogleins are calcium-dependent transmembrane glycoproteins of the desmosome that form an import component of the junction complexes of epithelial cells. Desmogleins are involved in maintaining the structural integrity of tissues. So far, four different desmogleins (Dsg1, Dsg2, Dsg3 and Dsg4) have been identified. OBJECTIVE: The purpose of this study was to observe the distribution pattern of desmoglein-3 in the fetal skin during development. METHODS: Skin was obtained from the sole, scalp and lip of 34 fetuses that ranged in age from 10 to 39 weeks of gestational age. Immunohistochemical staining was performed on the paraffin embedded tissue using anti-human monoclonal antibody against the desmoglein-3. RESULTS: The expression of desmoglein-3 in the epidermis appeared in the basal layer of the sole at the 10th week of gestation age. Thereafter, a stronger expression was noted in the middle layer of the sole and scalp epidermis. The basal layer had a stronger expression than did the other layers of the epidermis, followed by the middle and superficial layers. A stronger expression of desmoglein-3 in hair was noted in the outer root sheath, the bulge cells and the eccrine duct cells. The expression of desmoglein-3 in the lip mucosa was strong in both the basal and middle layers, while the skin side of the mucosa showed a stronger expression in basal layer. CONCLUSION: These results suggested that desmoglein-3 plays an important role in the development and differentiation of the epidermis and skin adnexa in the fetal stage, and especially in basal and suprabasal layers.
Desmogleins ; Desmosomes ; Epidermis ; Epithelial Cells ; Fetus ; Gestational Age ; Glycoproteins ; Hair ; Lip ; Mucous Membrane ; Paraffin ; Pregnancy ; Scalp ; Skin

BACKGROUND: Matrix metalloproteinases (MMPs) participate in extracellular matrix degradation and may play an important role in basal membrane damage in many dermatologic diseases. Recent studies implicated the importance of MMP-9 in the pathogenesis of bulla formation of bullous pemphigoid (BP). Various autoimmune bullous diseases are strongly associated with desmosome or hemidesmosome pathologies, and show an increased level of lesional MMP and exposed autoantigens from these structures. OBJECTIVE: This study evaluated the level of MMP-2, -3, and -9 in three types of autoimmune bullous disease [BP, pemphigus vulgaris (PV), pemphigus foliaceus (PF)] with the aim of investigating the role of MMPs in the pathogenesis of autoimmune bullous diseases. METHODS: Sample specimens were obtained from skin lesions of patients with BP (n=12), PV (n=10), and PF (n=12), and from normal controls (n=8). The immunohistochemical expression of MMP-2, -3, and -9 was analyzed and serum levels of MMP-2, -3, and -9 were measured by enzyme-linked immunosorbant assay (ELISA). The results were analyzed with reference to graded levels of clinical severity. RESULTS: Expression of dermal MMP-2, -3, and -9 were increased in BP, PV, and PF (p=0.036, 0.022, and 0.015, respectively). However, decreased expression of the three MMPs in the epidermis of skin lesions may have resulted from epidermal destruction. ELISA-determined serum levels of MMP-2, -3, and -9 increased in BP, PV and PF. Interestingly, MMP-2 was significantly increased in the sera of BP patients (p=0.015), consistent with the previous studies concerning the role of gelatinase (MMP-2 and -9) in the pathogenesis of BP. In BP patients, clinical severity was proportional to increased levels of MMP-2 in both skin lesions and and sera. CONCLUSION: The increased expression of MMP-2, -3, and -9 in skin lesions and sera may reflect the involvement of these enzymes in the mechanism of bulla formation in autoimmune bullous diseases including BP. In addition, expression of MMP and clinical severity may be closely connected.
Autoantigens ; Blister ; Desmosomes ; Epidermis ; Extracellular Matrix ; Gelatinases ; Hemidesmosomes ; Humans ; Matrix Metalloproteinases ; Membranes ; Pemphigoid, Bullous ; Pemphigus ; Skin

BACKGROUND: Desmogleins are transmembrane glycoproteins of the desmosome which provide mechanical strength to epithelial tissue. Desmogleins have so far, been implicated in several diseases such as pemphigus, striate palmoplantar keratoderma, 4S and squamous cell carcinomas. Skin cancer usually occurs in old age. And there are reports that the expression of desmogleins are increased in squamous cell carcinoma. However the role of desmogleins in skin aging has not yet been reported. OBJECTIVE: The purpose of this study was to investigate the expression of desmoglein 1 and 3 according to chronologic skin aging. METHODS: A total of 6 normal tissue samples from sun-protected skin of different age groups (from 34-year-old to an 84-year-old) and 1 squamous cell carcinoma tissue from a 72-year-old patient were taken. Western blotting and immunohistochemical staining were performed with anti desmoglein 1 and 3 antibodies. The expression of desmoglein 1 and 3 by Western blotting were calculated semiquantitatively by a densitometer. RESULTS: The expression of desmoglein 1 was 0.382 in the 34-year-old, 0.450 in the 45-year-old, 0.369 in the 56-year-old, 0.761 in the 65-year-old, 1.035 in the 77-year-old and 1.329 ODu/mm2 in the 84-year-old. The expression of desmoglein 3 was 0.830 in the 34-year-old, 0.984 in the 45-year-old, 1.029 in the 56-year-old, 1.534 in the 65-year-old, 1.714 in the 77-year-old and 1.878 ODu/mm2 in the 84-year-old. In immunohistochemical staining, the expression of Dsg1 increased from the basal layer to the granular layer and Dsg3 was expressed in the basal and suprabasal layers. CONCLUSION: The expression of desmoglein 1 and 3 were increased according to chronologic skin aging.
Adult ; Aged ; Aged, 80 and over ; Antibodies ; Blotting, Western ; Carcinoma, Squamous Cell ; Desmoglein 1* ; Desmoglein 3 ; Desmogleins* ; Desmosomes ; Glycoproteins ; Humans ; Keratoderma, Palmoplantar ; Middle Aged ; Pemphigus ; Skin Aging* ; Skin Neoplasms ; Skin*