Distinct types of abnormality in kinetic properties of three Darier disease-causing sarco(endo)plasmic reticulum Ca2+-ATPase mutants that exhibit normal expression and high Ca2+ transport activity.

The possible functional abnormalities in three different Darier disease-causing Ca(2+)-ATPase (SERCA2b) mutants, Ile(274) --> Val at the lumenal end of M3, Leu(321) --> Phe on the cytoplasmic part of M4, and Met(719) --> Ile in P domain, were explored, because they exhibited nearly normal expression and localization in COS-1 cells and the high ATPase and coupled Ca(2+) transport activities that were essentially identical (L321F) or slightly lower (I274V by approximately 35% and M719I by approximately 30%) as compared with those of the wild type. These mutations happened to be in Japanese patients found previously by us. Kinetic analyses revealed that each of the mutants possesses distinct types of abnormalities; M719I and L321F possess the 2-3-fold reduced affinity for cytoplasmic Ca(2+), whereas I274V possesses the normal high affinity.

Unique keratinization process in psoriasis: late differentiation markers are abolished because of the premature cell death.

The keratinization process in psoriasis is a unique phenomenon. We have proposed an organized system for keratinization in psoriasis based on the recognition of early and late differentiation markers combined with premature cell death. The early differentiation markers, such as involucrin, small proline-rich proteins (SPRR), cystatin A and transglutaminase l, are more conspicuously expressed in psoriasis, while the late differentiation markers, such as profilaggrin and loricrin, are abolished.

Epidermal lamellar granules transport different cargoes as distinct aggregates.

Lamellar granules (LG) of the epidermis appear as discrete round or oblong shaped granules in classical transmission electron micrographs, but a recent cryo-transmission electron microscopy study has claimed that LG are in fact branched tubular structures. LG contain various cargoes including lipids, hydrolytic enzymes, and several other proteins. It is not known whether there are any differences in the timing of expression among them and whether they are sorted into the granules individually or collectively.

Roxithromycin decreases ultraviolet B irradiation-induced reactive oxygen intermediates production and apoptosis of keratinocytes.

Background: In addition to their antimicrobial action, roxithromycin (RXM), a new 14-membrane macrolide antibiotics, have immunomodulatory, anti-inflammatory and anti-oxidative activity. Ultraviolet B (UVB) irradiation induces reactive oxygen intermediates and apoptosis of keratinocytes.

Objective: To examine the anti-apoptotic and anti-oxidative effect of RXM on UVB-irradiated keratinocytes.

Olmsted syndrome with squamous cell carcinoma of extremities and adenocarcinoma of the lung: failure to detect loricrin gene mutation.

Olmsted syndrome is an uncommon disorder of keratinization that presents mutilating palmoplantar keratoderma, periorificial hyperkeratosis, leukokeratosis and alopecia. We report a new case of this rare syndrome diagnosed in 48-year-old woman who developed several squamous cell carcinomas of limbs and adenocarcinoma of the lung. She has been followed up for about 40 years and osteolytic changes of the fingers and toes accompanied the keratinizing disorder and squamous cell carcinoma.

Application and limitations of three-dimensional reconstruction of the epidermal-dermal junction using electron microscopy.

Background: Anchoring fibrils were initially described as the arch-like structures that extend from the lamina densa to the sub-lamina densa. Keene et al. proposed a model in which the anchoring fibrils bridge structures called "anchoring plaques", and thus the three-dimensional (3D) structure of the anchoring fibrils remains somewhat controversial.

Activation of two caspase cascades, caspase 8/3/6 and caspase 9/3/6, during photodynamic therapy using a novel photosensitizer, ATX-S10(Na), in normal human keratinocytes.

Background/purpose: Photodynamic therapy (PDT) is a potent treatment for skin tumors. Although the therapeutic effect of PDT is supposed to be due to cellular cytotoxicity, the precise mechanism is still unknown. ATX-S10(Na) [13,17-bis(1-carboxypropionyl)carbamoylethyl-8-ethenyl-2-hydroxy-3-hydroxyiminoethylidene-2,7,12,18-tetramethylporphyrin sodium salt], a novel hydrophilic chlorin photosensitizer, shows good accumulation in tumors and is suitable for use in PDT.

1,25-dihydroxyvitamin D(3) increases human cystatin A expression by inhibiting the Raf-1/MEK1/ERK signaling pathway of keratinocytes.

The active form of vitamin D(3), 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D3), regulates proliferation and differentiation of keratinocytes. Cystatin A, a cysteine proteinase inhibitor, is a cornified cell envelope constituent and a differentiation marker of keratinocytes. In the present study, we examined the effect of 1,25(OH)(2)D3 on the expression of cystatin A of cultured normal human keratinocytes (NHK).

Pathophysiology of generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a serious dermatological disease characterized by fever, chills, rigors, and generalized pustule formation on the skin. Previous analyses in Japan have led to the proposal to divide GPP into two groups, one with a history of ordinary psoriasis (pso(+) GPP) and the other without a history of psoriasis (pso(-) GPP). Clinically the onset of the pustular outbreak is earlier in pso(-) GPP, which occurs more frequently after infections, whereas pso(+) GPP occurs more frequently following corticosteroid therapy.

Similarly potent action of 1,25-dihydroxyvitamin D3 and its analogues, tacalcitol, calcipotriol, and maxacalcitol on normal human keratinocyte proliferation and differentiation.

Background: The active vitamin D3 regulates proliferation and differentiation of epidermal keratinocytes. Recently topical vitamin D3, tacalcitol, calcipotriol, and maxacalcitol are widely used for psoriasis.

Objective: To examine the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on cultured normal keratinocytes (NHK) and compared its effect with those of various vitamin D3 analogues.

Loricrin keratoderma: a novel disease entity characterized by nuclear accumulation of mutant loricrin.

Loricrin is the major protein of the cornified cell envelope, a structure that replaces the plasma membrane during keratinocyte terminal differentiation. Recently, unique heterozygous, insertion mutations in the loricrin gene have been found to underlie certain congenital skin abnormalities, the phenotypes of which vary considerably. Clinically, these patients can be diagnosed as suffering from an ichthyotic variant of Vohwinkel's syndrome (VS), progressive symmetric erythrokeratoderma, or congenital ichthyosiform erythroderma born as a collodion baby.

CD4+ T-cells from peripheral blood of a patient with psoriasis recognize keratin 14 peptide but not 'homologous' streptococcal M-protein epitope.

Psoriasis has been recognized as an immunologically mediated inflammatory skin disease that has been associated with group A, beta-haemolytic streptococcal infections. Notably cross-reactive autoimmune mechanism, which is mediated by T cells reacting to epitopes that are common to streptococcal M-protein and keratin, has been proposed in psoriasis. In order to investigate this possibility, peptides corresponding to M-protein and human epidermal keratin, which share some amino acid sequence between them, were synthesized and tested for their ability to stimulate T-cells of patients with psoriasis.

Extracellular regulated kinase and c-Jun N-terminal kinase are activated in psoriatic involved epidermis.

Psoriatic skin shows markedly increased keratinocyte proliferation and altered differentiation with various abnormal signalling pathways. In the present study, we investigated the expression of mitogen-activated protein kinases in psoriatic skin. Immunohistochemical study showed increased extracellular regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) expression in the nuclei of involved epidermis.

Elafin, a secretory protein, is cross-linked into the cornified cell envelopes from the inside of psoriatic keratinocytes.

Elafin is a serine proteinase inhibitor highly expressed in psoriatic epidermal keratinocytes, but expressed scarcely, if at all, in normal skin. In addition to the proteinase inhibiting domain, elafin contains multiple transglutaminase substrate domains and has been identified as a constituent of the epidermal cornified cell envelope. It also contains a signal peptide sequence, and previous immunoelectron microscopy studies detected elafin in lamellar granules and also in the intercellular spaces.

Fibroepithelioma-like changes occurring in perianal Paget's disease with rectal mucinous carcinoma: case report and review of 49 cases of extramammary Paget's disease.

Background: Anogenital Paget's disease (PD) may be accompanied by varying degrees of epidermal hyperplasia. The histological changes can be reminiscent of fibroepithelioma of Pinkus.

Methods: We present a case of perianal PD associated with fibroepitheliomatous epidermal hyperplasia in a 76-year-old-man with an underlying rectal mucinous carcinoma.

Eccrine squamous syringometaplasia and syringomatous hyperplasia in association with linear scleroderma.

It is now well recognized that syringomatous hyperplasia with squamous syringometaplasia is a type of pseudoepitheliomatous hyperplasia responding to a variety of stimuli. We report a case of linear scleroderma with this process. Histopathology of the lesion showed numerous solid and cystic epithelial structures with squamous metaplasia within typical sclerodermatous skin lesions.

Aberrant expression of apoptosis-related molecules in psoriatic epidermis.

Apoptosis is a physiological form of cell death that is responsible for the deletion of cells. Epidermal keratinocytes are supposed to be regulated by cell proliferation and cell death leading to structural homeostasis. Psoriatic skin shows marked thickening of the epidermis, suggesting the imbalance of the homeostasis, which might be related to abnormal apoptotic process.

Ultraviolet B irradiation increases keratin 5 and keratin 14 expression through epidermal growth factor receptor of SV40-transformed human keratinocytes.

Keratin intermediate filaments are heteropolymers composed of type I and type II keratins. Ultraviolet B (UVB) irradiation induces keratin expression by keratinocytes. Using SV40-transformed human keratinocytes (SVHK), we investigated the effect of UVB irradiation on keratin expression.

Sequential reorganization of cornified cell keratin filaments involving filaggrin-mediated compaction and keratin 1 deimination.

The final step of keratinocyte differentiation, transition from the granular cells to the cornified cells, involves various post-translational modifications that include deimination of arginine residues. Major deiminated epidermal proteins are derived from K1. Two preferred deimination sites were identified in mouse K1, one in the V1 and the other in the V2 subdomains.