Malka Hochberg

Direct Antifungal Effect of Femtosecond Laser on Trichophyton rubrum Onychomycosis

Onychomycosis is caused by dermatophyte infection of the nail. Though laser energy has been shown to eliminate dermatophytes in vitro, direct laser elimination of onychomycosis is not successful due to difficulties in selectively delivering laser energy to the deeper levels of the nail plate without collateral damage. Femtosecond (fsec) infrared titanium sapphire lasers circumvent this problem by the nonlinear interactions of these lasers with biological media. This quality, combined with the deeply penetrating nature of the near‐infrared radiation, allows elimination of deeply seeded nail dermatopytes without associated collateral damage. Nail cuttings obtained from patients with onychomycosis caused by Trichophyton rubrum underwent fsec laser irradiation using increasing laser intensities with the focus scanned throughout the whole thickness of the nail specimen. The efficacy of the laser treatment was evaluated by subculture. Scanning electron microscopy was used to determine fsec laser‐induced collateral damage. We found that a fsec laser fluence of 7 × 1031 photons m−2 s−1 or above successfully inhibited the growth of the fungus in all samples examined, whereas laser intensities above 1.7 × 1032 photons m−2 s−1 affected the structure of the nail plate. Our findings suggest that T. rubrum‐mediated onychomycosis may be treated by fsec laser technology.

Expression of tyrosinase, MIA and MART-1 in sentinel lymph nodes of patients with malignant melanoma

Summary Background Regional lymph node status is an important predictor of survival in patients with malignant melanoma. Mapping of sentinel lymph nodes using sensitive molecular techniques has recently been introduced. Malignant melanoma is heterogeneous in terms of its biological, immunological and metastatic properties, and melanoma cells exhibit a polymorphous expression of tumour markers. Thus, assays that include multiple markers appear to be more sensitive than single‐marker assays.

Gene expression profiling of in vivo UVB-irradiated human epidermis.

Background: Several recent studies have employed microarray profiling to study UVB‐regulated gene expression in human skin. These studies are all based on UV‐irradiated cultured cells that differ substantially from the intact tissues they are supposed to imitate. The purpose of the present study was to analyze the differential expression of UVB‐regulated genes in intact human epidermis following in vivo UV irradiation.

Genomic-scale analysis of psoriatic skin reveals differentially expressed insulin-like growth factor-binding protein-7 after phototherapy

Background  Phototherapy is an effective therapy for psoriasis. The molecular mechanisms underlying its efficacy are not yet understood.

Increased prevalence of onychomycosis among psoriatic patients in Israel.

Published data on the prevalence of onychomycosis in psoriasis patients compared with healthy controls are controversial, We therefore conducted a prospective study of toenail onychomycosis, among 113 psoriatic and 106 healthy non-psoriatic subjects, selected from the normal population in the Jerusalem area in the period 2003-05. The results revealed a prevalence of 47.6% toenail onychomycosis among psoriatic patients, compared with 28.4% in normal controls (p=0.0054). Both gender and age affected the prevalence of onychomycosis in both psoriatic and healthy controls, with a higher prevalence in male and elderly subjects. The type and duration of psoriasis were also found to have an impact on the prevalence of onychomycosis. However, the body area involved did not affect the prevalence of onychomycosis in psoriatic patients. Approximately the same percentages of dermatophytes and yeasts were found in psoriatic patients as in healthy controls. However, a higher percentage of moulds was found in psoriatic patients.

Prevalence of Candida on the tongue and intertriginous areas of psoriatic and atopic dermatitis patients

Data in the literature regarding the prevalence of Candida in psoriatic and atopic dermatitis patients are controversial. We conducted a prospective study to determine the prevalence of Candida on the tongue, axillae and groin of psoriatic patients when compared with atopic dermatitis patients and normal controls. During the period 2003–2005, data were collected from 100 psoriatic patients, 100 patients with atopic dermatitis and 100 normal controls. Fungal test specimens for Candida were collected from the axillae, groin and tongue of each patient. There was no increase in the prevalence of Candida in intertriginous area of either psoriatic or atopic dermatitis patients. However, the prevalence of Candida on the tongue was significantly higher in psoriatic patients (32%) compared with atopic dermatitis (18%) (P = 0.024) and higher, although not significantly, than in normal controls (21%) (P = 0.08). Our study did not reveal higher prevalence of Candida in the axillae and groin of either psoriatic or atopic dermatitis patients. There was a higher prevalence of Candida on the tongue of psoriatic patients. The Candida of the tongue was asymptomatic and did not correlate with age, gender, type of psoriasis or severity of the disease, therefore we conclude that this is clinically irrelevant.

Molecular detection of MART-1, tyrosinase and MIA in peripheral blood, lymph nodes and metastatic sites of stage III/IV melanoma patients.

Melanoma lesions that develop in the same patient at different times or simultaneously at different locations may differ antigenically, because malignant melanoma is heterogeneous in terms of its biological, immunological and metastatic properties. The objective of this study was to characterize the molecular profiles of melanoma cells in peripheral blood, lymph nodes and metastatic tissues, employing the messenger RNA (mRNA) expression of tyrosinase, melanoma-inhibiting activity (MIA) and melanoma antigen recognized by T cells-1 (MART-1) as markers. Samples of cells propagated from metastatic sites were obtained from 17 stage III/IV melanoma patients and assayed by reverse transcriptase-polymerase chain reaction (RT-PCR), using specific primers for each marker. In eight patients, marker profiles were analysed in simultaneously obtained specimens of peripheral blood, lymph nodes and metastatic tissues originating from the same patient. Tyrosinase, MIA and MART-1 were expressed in 59%, 76% and 76% of the metastases, respectively. Simultaneously obtained specimens of peripheral blood, lymph nodes and metastatic tissues showed a high degree of homogeneity: 60%, 75% and 20% for tyrosinase, MIA and MART-1, respectively. Our findings suggest that the rather homogeneous expression pattern found in different tumour sites analysed in the same patient is of potential prognostic and therapeutic importance. Furthermore, melanoma lesions may be negative for the expression of antigens such as MART-1, and discrepancies in expression patterns between peripheral blood and metastatic tissues may occur, especially for this marker. Finally, our findings support the notion that molecular screening using an RT-PCR approach is appropriate in this kind of investigation.

Insulin-like growth factor-binding protein-7 (IGFBP7) transcript: A-to-I editing events in normal and cancerous human keratinocytes

Non-melanoma skin cancers (NMSC) are the most common malignancies in caucasians worldwide. Insulin-like growth factor-binding protein-7 (IGFBP7) was suggested to function as a tumor suppressor gene in several cancers, and to play a role in the proliferation of keratinocytes. A-to-I RNA editing is a post-transcriptional mechanism frequently used to expand and diversify transcriptome and proteome repertoire in eukaryotic cells. A-to-I RNA editing can alter codons, substitute amino acids and affect protein sequence, structure, and function. Two editing sites were identified within the IGFBP7 transcript. To evaluate the expression and editing of IGFBP7 mRNA in NMSC compared to normal epidermis. We examined the expression and mRNA editing level of IGFBP7 in 22 basal cell carcinoma (BCC), 15 squamous cell carcinoma (SCC), and 18 normal epidermis samples that were surgically removed from patients by the Mohs Micrographic Surgery procedure. We studied the effect of IGFBP7 editing on an immortalized HaCaT keratinocyte cell model. IGFBP7 mRNA is over expressed in BCC and SCC compared to normal epidermis. Moreover, the IGFBP7 transcript is highly edited in normal epidermis, but its editing is significantly reduced in BCC and SCC. The edited form of IGFBP7 can inhibit proliferation and induce senescence in cultured keratinocytes. This study describes for the first time A-to-I editing in the coding sequence of a tumor suppressor gene in humans, and suggests that IGFBP7 editing serves as a fine-tuning mechanism to maintain the equilibrium between proliferation and senescence in normal skin.

Prevalence of tinea pedis in psoriasis, compared to atopic dermatitis and normal controls - a prospective study

There are discrepancies in the literature regarding the prevalence of tinea pedis in psoriasis. The aim of this investigation was to conduct a cross‐sectional study of the prevalence of tinea pedis in psoriasis compared to atopic dermatitis patients and normal controls. We enrolled 232 psoriatic patients, 190 atopic dermatitis patients and 202 normal controls, between the years 2010 and 2013. The prevalence of tinea pedis was 13.8% in psoriasis patients, not significantly different from that in atopic dermatitis patients 8.4% (P = 0.092)), but significantly higher than in normal controls 7.4% (P = 0.043). Both gender and age affected the prevalence of tinea pedis in psoriasis and normal controls, while only age affected the prevalence of tinea pedis in atopic dermatitis. Regarding gender, there was higher prevalence of tinea pedis in men: 19.1% (P = 0.019) in psoriasis and 12.1% (P = 0.013) in normal controls. Age affected the prevalence of tinea pedis in normal controls (P < 0.001), psoriasis patients (P = 0.001) and atopic dermatitis patients (P = 0.001), with higher prevalence with increasing age. Trichophyton rubrum was the most common species in psoriasis (71.9%), atopic dermatitis (75.0%) and normal controls (73.3%). Our study found a relatively high prevalence of tinea pedis among psoriasis patients.

Tropism of herpes simplex virus type 1 to nonmelanoma skin cancers

Background  Current treatments for nonmelanoma skin cancer include surgery, Mohs micrographic surgery, radiation, cryosurgery, photodynamic therapy, local chemotherapy and application of immunomodulators such as imiquimod. However, all have a 5‐year recurrence rate of 1–40%. Gene therapy for the treatment of skin cancers is a promising new approach, as delivery of the vectors to the skin is simple and safety issues can be properly addressed.