Biomedical subjects

Sohaila Joubeh

Publications and source records attributed to Sohaila Joubeh.

4 recordsLinked to original sources

PubMed2004

Differential structural properties and expression patterns suggest functional significance for multiple mouse desmoglein 1 isoforms.

The four isoforms of desmosomal cadherin desmogleins (Dsg1-4) are expressed in epithelial tissues in a differentiation-specific manner. Extensive sequencing of the human genome has revealed only one copy of the Dsg1 gene. However, we recently cloned two novel additional mouse Dsg1 genes, Dsg1-beta and -gamma, which flank the original Dsg1-alpha on chromosome 18. Sequence conservation between the Dsg1 isoforms diverged significantly at exon 11, particularly in the region that encodes for the extracellular anchoring (EA) domains. Computational analysis revealed very low hydrophilic potential of the Dsg1-gamma EA compared with the corresponding sequences of Dsg1-alpha and -beta, suggesting that the Dsg1-gamma EA domain may have a stronger affinity to the cell membrane. We generated antibodies using synthetic peptides or recombinant proteins localized within the EA domains. These antibodies were tested for their specificity and were then used to demonstrate expression of Dsg1 isoforms in various tissues. In the epidermis, all Dsg1 isoforms were differentially expressed in the differentiating cell layers. In the hair follicle, all Dsg1 isoforms were present throughout the entire process of its development and cycling but the expression of Dsg1 isoforms is subject to significant hair cycle-dependent changes. Dsg1-beta and -gamma, but not Dsg1-alpha, were detected in the sebaceous gland epithelium and the stratified epithelium of the stomach. Finally, Dsg1-alpha and Dsg1-beta, but not Dsg1-gamma, are proteolytically cleaved by exfoliative toxin A. These results suggest that the developmental complexity of mouse tissues, including skin and hair, may play a significant role in the evolutionary driving force to maintain multiple Dsg1 genes in mouse.

Amino Acid Sequence↗

PubMed2003

Immunofluorescence analysis of the basement membrane zone components in human anagen hair follicles.

The ultrastructure and constituent components of the basement membrane zone (BMZ) of the interfollicular epidermis have been well characterized. However, little is known about the junctions between dermal papilla and the surrounding epithelial cells of the hair bulb, as well as those junctions between connective tissues and epithelial cells outside the hair follicle. In the present study, immunofluorescence was used to determine the expression of various BMZ components, particularly plectin, BP230, BP180, alpha6beta4 integrin, laminin 5 and type VII collagen, in anagen hair follicles from human scalp. All the BMZ components examined showed essentially the same immunofluorescence staining pattern. Specifically, staining of the upper portion of the hair follicle demonstrated expression of all BMZ components with a labeling intensity similar to that found in the interfollicular epidermis. Staining in the lower portion of the hair follicle, however, was markedly different: all the BMZ components showed a gradual decrease in staining intensity. Particularly, outside the hair bulb, the linear staining was diminished and even discontinuous in some areas. Finally, between dermal papilla and epithelial cells inside the hair bulb, there was a strong immunoreactivity for all the BMZ components except for BP230, which was completely negative. The present study also confirmed a previous reported ultrastructural finding that hemidesmosomes are not apparent in the hair bulb's exterior BMZ nor in the dermal papilla junctions. Instead, peculiar cloudy materials were seen in both the lamina densa and the adjacent epithelium outside the hair bulb. Taken together, the diminished expression of all the BMZ components outside the hair bulb, as well as the complete absence of BP230 at the dermal papilla junction, seem to be responsible for the incomplete ultrastructure of hemidesmosomes in these regions. Furthermore, the results in the present study led us to speculate that the expression of BMZ components inside and outside the hair bulb are markedly decreased in the transient regions of the hair follicle as compared with their expression in the permanent region, signified by the upper portion of the hair follicle. When the hair follicle moves upward in catagen or downward in anagen, the complete structure of the hemidesmosome may stabilize the upper portion to the surrounding connective tissues, while the incomplete hemidesmosome may facilitate the movement of the transient region.

Autoantigens↗

PubMed2003

Desmoglein-3 is a target autoantigen in spontaneous canine pemphigus vulgaris.

Pemphigus vulgaris (PV) is an autoimmune blistering skin disease of humans and companion animals. In human patients, PV is associated with the production of IgG autoantibodies specific for keratinocyte desmosomal glycoproteins of the cadherin family. The purpose of this study was to determine whether antikeratinocyte IgG autoantibodies were present in the skin and serum of dogs with PV, and also to identify the canine PV autoantigen(s) targeted by circulating autoantibodies. Eleven dogs were selected because of the microscopic demonstration of suprabasal epithelial acantholysis. Direct immunofluorescence revealed the presence of IgG autoantibodies bound to the membrane of keratinocytes in skin biopsy specimens of 8/9 dogs (89%). Using indirect immunofluorescence, serum-circulating IgG autoantibodies were found in 10/11 (91%) and 5/11 (45%) dogs, using normal canine gingiva and cultured canine oral keratinocytes, respectively. By immunoblotting using cultured canine oral keratinocyte protein lysates, IgG autoantibodies from 7/9 (78%) tested dogs recognized a 130-kDa antigen that comigrated with that identified by rabbit polyclonal antibodies raised against desmoglein-3. This 130 kDa antigen was confirmed to represent the canine equivalent of human desmoglein-3 by immunoprecipitation-immunoblotting. The results of these studies provide evidence that the canine desmoglein-3 homologue is a major autoantigen in dogs with PV. These observations further establish spontaneous canine PV as a natural model for research on pathogenesis, etiology and novel therapeutic approaches for this disease of humans.

Animals↗

PubMedDate not supplied

Erysipeloid cutaneous leishmaniasis: treatment with a new, topical, pure herbal extract.

Fourteen consecutive cases of erysipeloid cutaneous leishmaniasis were seen and evaluated. There were 13 females and one male patient with a mean age of 59 years. Diagnosis was based on clinical grounds and the presence of amastigotes in the lesions. Patients were divided into acute and chronic groups, with chronicity being defined as a disease duration of more than a year. All cases were treated with a fresh preparation of a herbal mixture, namely "Z-HE". The paste was applied once daily for 5 consecutive days and thereafter every 2 weeks, as needed, for a maximum period of 3 months. Two patients didn't appear for their regular follow up, the remaining 12 cases were followed up for more than a year after termination of therapy. Eleven (92%) of patients had complete healing in a matter of 1 to 7 months with no relapse after 12 months of follow up. In spite of a successful initial clinical response, the remaining one patient with the acute type of ECL had a subsequent relapse. Otherwise the acute and chronic cases had similar responses to therapy and outcome. No drug related side effect was noted. The high success rate, low cost, ease of preparation, and lack of toxicity makes "Z-HE" a promising new drug. Further investigations are needed to illuminate its mechanism(s) of action and also controlled trials are recommended to confirm its efficacy.

Administration, Topical↗