The effect of anti-interleukin (IL)-4/-13 treatment, dupilumab, on allergic diseases and the resulting various unexpected phenomena have been reported in the literature. The clinical features of mycosis fungoides (MF) with multiple erythematous lesions are similar to those of atopic dermatitis (AD). Thus, anti-IL-4/-13 therapy may be erroneously administered to patients with MF with features similar to those of AD. This report is the first to describe a case of MF diagnosed after administration of dupilumab for AD. CASE REPORTA 58-year-old man had had AD since early childhood. Although remission had occurred in adolescence, eczema had appeared on his trunk and limbs at the age of 47 years. He presented to a dermatologist and was administered topical corticosteroid ointment, betamethasone butyrate propionate, based on the diagnosis of recurrent AD. In 2013 the patient was referred to our university for treatment of a carcinoma of the maxillary sinus using chemoradiotherapy. Treatment was successful. Subsequently, the patient continued treatment for AD in our department. The cutaneous eruption was somewhat controlled by topical treatments; however, at times he experienced intense itching ( Fig. 1). He reported a history of allergic rhinitis, conjunctivitis and asthma. Given the severity of his AD, treatment with dupilumab 600 mg, subcutaneously was initiated on the first day, followed by 300 mg every 2 weeks in 2018. Serum examination prior to administration revealed elevated levels of thymus-and activation-regulated chemokine (TARC, 4,634 pg/ ml; normal range: < 450 pg/ml), IgE (1,280 IU/ml; normal range: < 250 IU/ml), and lactate dehydrogenase (LDH, 269 U/l; normal range: 124-224 U/l). The eosinophil count was within normal limits. The Eczema Area and Severity Index (EASI) was 34.4, while the Dermatology Life Quality Index (DLQI) was 8. During treatment with dupilumab, the faint erythematous lesions on the face and trunk became more obvious, despite continuous application of the topical steroid (Fig. 2). After 1 month, the EASI and DLQI were slightly decreased (29 and 6, respectively); however, there was no improvement in pruritic symptoms. Laboratory tests revealed that TARC, IgE, and LDH levels were 3,948 pg/ml, 924 IU/ml, and 287 U/l, respectively. Owing to exacerbation of the erythematous lesions, skin biopsy of the erythematous macule on the trunk was performed. Histopathology showed band-like atypical lymphocytic infiltration into the dermis. Atypical epidermotropic lymphocytes without spongiosis were observed in the epidermis, which formed Pautrier's microabscess (Fig. 3). Fig. 1. (a) Erythematous lesions on the face. (b) Poikiloderma lesions accompanied by papules and nodules on the back. Written permission from the patient is given to publish these photos. Fig. 2. (a) Face and (b) back after 1 month of treatment with dupilumab.Written permission from the patient is given to publish these photos. Fig. 3. Histopathology of the biopsy specimen from the erythematous lesion on the chest shows lymphocytic infi...
Fertilization of pig oocytes was performed in vitro in modified Tyrode's media in which either HEPES or bicarbonate/CO2, or both, were included as buffer systems; caffeine (2 mM) was also included in some of the media because it is a reported stimulant of fertilization. The composition of the bicarbonate-containing media was designed so as to maintain the same pH and osmolality as bicarbonate-free media. The inclusion of bicarbonate during gamete co-incubation in caffeine-containing medium led to high levels of fertilization (66% of 238 mature oocytes were fertilized). However, essentially no fertilization occurred if bicarbonate was replaced with HEPES (0.7% of 146 oocytes were fertilized; significantly different, P < 0.001). Inclusion of HEPES in bicarbonate-containing medium during gamete co-incubation did not affect fertilization, showing that HEPES did not exert an inhibitory effect. Omission of bicarbonate during sperm preincubation also did not affect fertilization. If caffeine was included in bicarbonate-containing medium, 73% of 311 oocytes were fertilized whereas if caffeine was omitted only 14% of 326 oocytes were fertilized (significantly different, P < 0.001). In the absence of bicarbonate, when fertilization was very low, caffeine had no stimulatory effect. The results indicate that bicarbonate is essential for pig fertilization in vitro, but that caffeine exerts a synergistic stimulatory effect.
Hyperacute rejection (from pig to human) is thought to result from activation of complement initiated by the binding of host natural antibodies to α‐galactosyl (α‐Gal) epitopes of donor endothelial cells. However, α‐Gal epitope shares a common precursor with H antigen in humans. This means that H antigens as well as α‐Gal epitopes are synthesized in a competitive manner by different enzymes. We thought that it would be possible to convert α‐Gal epitopes into H antigens by introducing cDNA of α(1,2)‐fucosyltransferase (α1–2FT) into porcine cells, and so, pig embryos were microinjected with αl‐2FT cDNA. Transgenic pigs that carried α1–2FT were thus established. Cytotoxicity of fibrocytes derived from skin of transgenic pig was measured by 51Cr release assay, which showed that H antigen‐expressing cells were significantly resistant to a challenge with human sera. These experiments indicate that our method provides a new strategy which contributes to a successful discordant xenotransplantation.
A transgenic pig carrying MMTV/v-Ha-ras was produced by microinjection of DNA into pronuclear stage embryos. Reproductive technologies, such as superovulation, insemination methods and synchronization of recipients were also investigated to establish the efficient systems to obtain pronuclear stage embryos and transgenic pigs aiming at improving efficiency of the protocol for producing transgenic pigs. Integration of the transgene was detected by Southern hybridization analysis in one female among 29 piglets which had been born after transfer of 195 DNA-injected embryos to 8 recipients. Expression of the transgene was detected by RT-PCR in 8 of 17 organs of the founder transgenic pig examined. The transgenic pig transmitted the transgene to 42.3% of 26 offspring. However, development of tumour was not found either in the founder or its progeny during the observation period for 30 and 1-8 months, respectively. The average number of ova collected from donors superovulated with 1500 IU eCG was significantly higher than the number collected from gilts which were superovulated with 1000 IU (26.3 vs 6.8, P<0.05). Donors served by artificial insemination yielded nearly the same number of embryos per head as those mated naturally (14.8 vs 16.1). Recipients of which the estrus was synchronized through administration of either 1500 or 750 IU eCG gave rise to pregnancies (5/5 vs 3/4). These data indicate that transgenic pigs carrying activated oncogene can be produced, though induction of the developmental disorders is yet to be investigated.
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