Klilah Hershko

The Inhibitor of Apoptosis Protein Livin (ML-IAP) Plays a Dual Role in Tumorigenicity

The inhibitor of apoptosis protein (IAP) family can inhibit apoptosis induced by a variety of stimuli. We and others previously described the IAP Livin (ML-IAP). We found that Livin is unique among the IAP members as, on a strong apoptotic stimulus, it is specifically cleaved by caspases to produce a truncated protein with paradoxical proapoptotic activity (tLivin). We also showed that Livin encodes two splicing variants, termed Livin alpha and beta, with diverse antiapoptotic effects in vitro. In this study, we compared the Livin isoforms in vivo. An animal model was established and the effects of Livin alpha and beta on the initiation and development of tumors were compared. In the animal model, Livin alpha promotes tumor initiation in comparison with control. Interestingly, the growth of tumors originating from cells expressing Livin beta was inhibited. In these tumors, Livin beta was cleaved and produced a high level of the proapoptotic tLivin beta that repressed tumor development. When we eliminated the proapoptotic effect of Livin beta by point mutations, the resulting antiapoptotic Livin beta mutants contributed to tumor progression. In terms of mechanism, we show that Livin beta tumors develop only in mice lacking natural killer (NK) cell activity. Thus, from the animal model, we can conclude that Livin plays a major role in tumorigenicity and that NK cells induce cleavage of Livin to its proapoptotic truncated protein that in turn inhibits tumor growth. Therefore, Livin and tLivin may serve as potential targets for cancer therapy.

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.

Exploring the mango-poison ivy connection: the riddle of discriminative plant dermatitis.

A relationship between sensitivity to poison oak or poison ivy and mango dermatitis has been suggested by previous publications. The observation that acute allergic contact dermatitis can arise on first exposure to mango in patients who have been sensitized beforehand by contact with other urushiol‐containing plants has been documented previously. We report 17 American patients employed in mango picking at a summer camp in Israel, who developed a rash of varying severity. All patients were either in contact with poison ivy/oak in the past or lived in areas where these plants are endemic. None recalled previous contact with mango. In contrast, none of their Israeli companions who had never been exposed to poison ivy/oak developed mango dermatitis. These observations suggest that individuals with known history of poison ivy/oak allergy, or those residing in area where these plants are common, may develop allergic contact dermatitis from mango on first exposure. We hypothesize that previous oral exposure to urushiol in the local Israeli population might establish immune tolerance to these plants.

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.

Mutations in lipase H cause autosomal recessive hypotrichosis simplex with woolly hair

BACKGROUND Mutations in lipase H (LIPH) are a rare cause of autosomal recessive hypotrichosis (HT) simplex. OBJECTIVE In this study, we investigated the clinical and molecular basis of HT simplex with woolly hair in 3 nonrelated families. METHODS Three families of Jewish, Arab Muslim, and Italian origin that presented with HT with woolly hair were studied. The phenotype was confirmed by clinical, microscopic, and histologic examination. Polymorphic microsatellite genotyping and direct automated DNA sequencing of the LIPH gene were used to identify the mutations in our probands. RESULTS All patients had woolly hair since birth. At presentation, scalp hair density was reduced or normal. Sequencing of the LIPH gene revealed two homozygous mutations: a large recurrent 90-base pair duplication mutation in exon 2 in the Jewish and Arab families, and a novel deletion/insertion mutation in exon 4 in the Italian family. LIMITATIONS Only 3 families were studied. CONCLUSION Mutations in LIPH result in variable degrees of HT. Woolly hair is an essential component of the clinical spectrum. A hot spot in the LIPH gene may be c.280_369dup in exon 2.

Herpes simplex virus infection in a hyper-IgE patient: appearance of unusual mass lesions.

A 7-year-old girl presented with large soft masses rising from the nostril and from behind the ear. She had previously been diagnosed as suffering from hyper-IgE syndrome. The presence of herpes simplex virus infection within these lesions was confirmed by biopsy and immunohistochemical studies. The mass lesions did not respond to antibacterial therapy with cefazolin, but improved promptly under antiviral therapy with acyclovir. Immunological studies revealed a mild decrease in the CD4 cell population. Based on our results and on the relevant literature we propose an immunological mechanism for this unique manifestation of herpes simplex virus infection in hyper-IgE syndrome.

AISI 316L Stainless-Steel Ear Piercing Post Assembly Does Not Cause Dermatitis in Nickel-Sensitive Subjects

Twenty-three female and 2 male subjects, documented to be sensitive to nickel by history and diagnostic patch testing, were pierced with American Iron Steel Institute (AISI) 316L stainless-steel ear piercing post assemblies (The Ear Piercing Manufacturers of Europe, UK), AISI 316L having a specification that includes a nickel content of between 10 and 14%. After piercing, the subjects were examined on days 7, 14, 30 and 42. Seven of the ear piercing post assemblies collected at random from the subjects at the end of the study and 10 unused post assemblies selected at random were analysed for nickel content and release. None of the nickel-sensitive patients showed signs of nickel dermatitis during the study. The nickel content of the ear piercing post assemblies collected from patients was reported as being between 11.5 and 12.9%, and the calculated rate of nickel release was below the detection limit of the method, thus recorded at <0.05 µg/cm2/week. By comparison, the nickel content of the unused post assemblies was reported to be between 9.93 and 10.5%, and the calculated rate of nickel release was between 0.11 and 0.21 (mean: 0.15) µg/cm2/week. These results suggest that the AISI 316L stainless-steel ear piercing post assemblies do not elicit adverse reactions to nickel in previously sensitized subjects.