Alexander Zemtsov

Association between basal, squamous cell carcinomas, dysplastic nevi and myotonic muscular dystrophy indicates an important role of RNA-binding proteins in development of human skin cancer

Myotonic muscular dystrophy (MMD) is caused by an abnormal function of RNA-binding proteins (RBP) resulting in DNA spliceopathy. A case of a patient, with MMD multiple basal and squamous cell carcinomas and dysplastic nevi, is described. The association between MMD and non-melanoma skin cancer has been reported before; however, this association was described before the genetic defect of myotonic dystrophy has been fully elucidated. The author proposes a genetic mechanism on how abnormal function of RBP can result or contribute to the development of human skin cancer and propose an explanation for this association between MMD and cutaneous carcinogenesis.

Identification and Activity of Cytosol Creatine Phosphokinase Enzymes in Normal and Diseased Skin

Phosphocreatine molecules (PCR) in skin regenerate adenosine triphosphate and help cutaneous tissue survive ischemia associated with skin flaps, grafts, and hair transplantation procedures. In addition, PCR concentration in psoriasis is elevated many times above normal, indicating either overproduction of PCR by mitochondrial creatine phosphokinase (CPK) enzymes or a defect in cytosol CPK enzymatic activity. Skin CPK isoenzymes, before this study, have not been identified. Herein, for the first time, cytosol CPK enzymatic activity was measured in normal and psoriatic, involved and un-involved skin, skin tumors, and mouse skin and keratinocyte cell cultures. Creatine phosphokinase MM is the major isoenzyme in normal, un-involved psoriatic and mouse skin. Total CPK enzymatic activity was increased in psoriasis and skin tumors. These data clearly indicate that increased PCR concentration in a psoriatic skin is not a result of decreased cytosol CPK enzymatic activity.

Livedo reticularis as an initial clinical manifestation of gemcitabine-induced hemolytic uremic syndrome

with ulcerations on the extensor surfaces of fingers. Furthermore, Barzegar et al. reported a case of EED with verrucous surface on palms and soles. Dapsone was effective in the Barzegar case, but not in the Soubeiran case. In our case, single treatment with either dapsone or cyclosporin was not effective, but the combination was remarkably effective. Dapsone shows scavenger effect against the hydroxyl oxygen radical and suppressive effect on the production of interleukin (IL)-1, IL-6 and tumor necrosis factor-a from macrophages. Cyclosporin suppresses the production of IL-2 and c-interferon from T cells by its inhibitory effect on cytotoxic T cells. Combination of the two drugs might show additive or synergistic effect and could be alternative modalities for recalcitrant cases. The marked fibrosis of the chronic lesion is usually resistant against the dapsone treatment, for which surgical excision is recommended. Although firm nodules still remained on the soles in our case, the patient was satisfied showing no problem in daily life without the surgical maneuver. Erythema elevatum diutinum associated with liver transplantation was reportedly improved by reduction of cyclosporin dose. On the other hand, cyclosporin was effective for the EED lesions of our case. Cyclosporin upregulates transforming growth factor-b expression, which results in the increased extracellular matrix protein in endothelial cells. Cyclosporin was effective for relatively early ulcerated lesions but not firm old lesions in our case. The pathogenesis of EED is unknown at present. Although it is occasionally associated with immune-mediated, and hematological abnormal conditions, such as monoclonal IgA gammopathy, multiple myeloma, lymphoma and HIV infection, no such comorbidities was detected in our case.

Topically applied growth factors change skin cytoplasmic creatine kinase activity and distribution and produce abnormal keratinocyte differentiation in murine skin

Background/purpose: The skin has a functional and active phosphocreatine (PCR)/creatine kinase (CPK) system that regenerates adenosine triphosphate energy reserves during periods of ischemia. The objective of this study was to evaluate how topically applied growth factors affect CPK activity and distribution, and what histological changes growth factors induce in murine skin.

ISDIS President's welcome address to Skin Research and Technology

HE ENORMOUS contributions of molecular biology T techniques in elucidating the etiology and pathogenesis of skin diseases are well appreciated in the dermatological community (1). I hope that the truly revolutionary changes occurring in computer science, digital imaging and bioengineering fields, will have a similar impact on dermatological science and find numerous clinical applications. It is not beyond the realm of reality that in the next decade, image cytometry and related imaging techniques will allow dermatopathologists to differentiate between early patches of mycosis fungoides and parapsoriasis, and to improve the pathologist’s ability to diagnose early melanoma and its precursory lesions. Epiluminescence microscopy and computer analysis of skin lesions utilizing various algorithms should improve the ability of the practicing dermatologist to detect melanomas. Computerized total body imaging will help manage patients with numerous suspicious melanocytic lesions, and telemedicine techniques are already helping US rural physicians to manage their patients with dermatological problems. Skin MRI and ultrasonography are expected to become valuable diagnostic techniques that will help dermatologic and plastic surgeons to determine, preoperatively, the tumor depth, involvement of crucial underlying anatomical structures, and to detect tumor recurrence under skins flaps and grafts. High resolution MRI (utilizing skin surface coil) and upper high frequency ultrasound, confocal microscopy, MR, and ultrasound microscopy, are very promising newly emerging techniques. Magnetic Resonance Spectroscopy (MRS) appears to be well suited to monitor, non-invasively, survival of skin flaps and disease activity in patients with psoriasis, connective tissue diseases, and leg ulcers. Furthermore, MRS in conjunction with other biochemical techniques may help us to better understand the pathophysiology of skin disorders. Cosmetic and skin bioengineering scientists have a difficult task of developing new scientifically valid in vitro skin toxicology techniques in order to be in compliance with the European Parliament Cosmetic Directives that ban animal use experiments. I am very honored, and humbly accept the responsibility of being a North American co-editor of this journal. I am delighted that Dr. William van Stoecker was elected to succeed me as President of The International Society for Digital Imaging of Skin. I would like to thank him and Drs. Douglas Perednia, Jean Luc Leveque and Matthew Fleming for helping me to organize the society. I would also like to thank Professors Cuono, Maibach, Kligman, Neldner, Jorrizzo, Dobson, Bergfeld, Wolff, and Tyring for their support and encouragement. My final and greatest gratitude goes to Dr. Jrargen Serup and Munksgaard Publishing House, who made this journal a reality.