Thrombomodulin exerts cytoprotective effect on low-dose UVB-irradiated HaCaT cells.

Thrombomodulin (TM) is an endothelial cell surface anticoagulant glycoprotein that performs antimetastatic, angiogenic, adhesive, and anti-inflammatory functions in various tissues. It is also expressed in epidermal keratinocytes. We found that a physiological dose (10mJ/cm(2)) of mid-wavelength ultraviolet irradiation (UVB) significantly induced TM expression via the p38mitogen-activated protein kinase (MAPK)/cyclic AMP response element (CRE) signaling pathway in the epidermal keratinocyte cell line HaCaT; this shows that TM regulates the survival of HaCaT cells. SB203580, a p38MAPK inhibitor, significantly decreased TM expression and the viability of cells exposed to UVB. Furthermore, overexpression of TM markedly increased cell viability, and it was abrogated by TM small interfering RNA (siRNA), suggesting that TM may play an important role in exerting cytoprotective effect on epidermal keratinocytes against low-dose UVB.

MRI studies of spinal visceral larva migrans syndrome.

We report serial MR findings in four patients with myelitis caused by visceral larva migrans syndrome due to Toxocara canis or Ascaris suum infection. MR imaging revealed spinal cord swelling with or without gadolinium enhancement in three patients. T2-weighted images showed high signal intensities preferentially located in both lateral and posterior columns. Antihelmintic and corticosteroid treatment yielded improvement in neurologic deficits and spinal lesions. However, one patient with T. canis infection relapsed associated with reappearance of MRI abnormalities.

Hyper nuclear acetylation (HNA) in proliferation, differentiation and apoptosis.

Coactivators such as cyclic AMP-response-element binding protein (CREB)-binding protein (CBP) and p300/CBP associated factor (P/CAF) play a crucial role in coordinating and cointegrating eukaryotic transcription. One of the recent paradigms in the eukaryotic transcription field is the finding of molecular basis of coactivator function. The well characterized coactivators such as CBP and P/CAF have been proposed to coactivate/cointegrate gene expression with many transcription activators through two mechanisms. One is complex formation with the components with basal transcriptional machinery. Another is its intrinsic and associated enzymatic activity, which transfers an acetyl-base to the epsilon ( epsilon ) portion of lysine-residues in histones and certain nuclear proteins (factor acetyltransferases; FATs), such as p53, lymphoid enhancer-binding factor (LEF), and transcription factor IIE (TFIIE), which often results in increased transcriptional activity. Recently, the status of hyper nuclear acetylation (HNA) has been thought to influence proliferation, differentiation and apoptosis. Furthermore, recent reports showed that histone acetyltransferase (HAT) activity is increased in human disease, such as cancer and atherosclerosis, and studies have shown associations between nuclear acetylation/deacetylation and cell proliferation/differentiation.

Pseudoxanthoma elasticum (PXE)-like calcification in adult dermatomyositis.

A case of pseudoxanthoma elasticum (PXE)-like calcification in adult dermatomyositis (DM) is described. The patient was a 38-year-old woman with a history of dermatomyositis for 3 months. Yellowish, hard, papulo-plaque lesions, which looked like those of pseudoxanthoma elasticum, were noted on her left axilla. Calcium deposition was confirmed by X-ray, histopathological, and electron microscopic examinations. Histopathological and histochemical examinations showed acicular calcium deposition in the middle and deep dermis surrounded by mucin. Electron microscopic examination revealed that the calcium deposition was not on collagen fibers. These morphological features were distinct from those of PXE. We proposed the possibility that degenerated mucin or degenerated elastic fiber might result in subsequent calcium deposition in reticular calcinosis in adult DM. The calcification clinically disappeared without any specific treatment except for prednisolone and cyclophosphamide.

Treatment of psoriatic arthritis with granulocyte and monocyte adsorption apheresis.

Granulocyte and monocyte adsorption apheresis (GCAP) is a new extracorporeal apheresis treatment modality that removes pathogenic granulocytes. Recently, we found that GCAP is useful for treating pyoderma gangrenosum and pustular psoriasis. We thought that this treatment may also be effective for treating other disorders attributable to activated granulocytes and studied the efficacy of GCAP in 4 patients with psoriatic arthritis. Treatment with GCAP resulted in remarkable clearing of joint pain, suggesting that GCAP is valuable for treating arthritis as well as skin disorders. We present a detailed description of these patients and this novel therapy.

Treatment of pustular psoriasis with granulocyte and monocyte adsorption apheresis.

We studied the efficacy of granulocyte and monocyte adsorption apheresis in 2 patients with pustular psoriasis, one localized, the other generalized. Treatment with granulocyte and monocyte adsorption apheresis resulted in remarkable clearing of the skin lesions, suggesting that this therapy is a valuable tool for treating patients with intractable skin diseases attributable to activated granulocytes. We present detailed descriptions of these patients and this novel therapy.

Possible role of transcriptional coactivator P/CAF and nuclear acetylation in calcium-induced keratinocyte differentiation.

Several nuclear factors, called coactivators, such as CREB (cAMP response element binding protein)-binding protein (CBP) and p300/CBP associated factor (P/CAF), have intrinsic histone acetyltransferase (HAT) activity. Recent studies have shown that, in addition to histones, transcriptional regulatory molecules are also targets of HATs, and nuclear acetylation is thought to be involved in several biological events. We observed that a high concentration of calcium induced HAT activity in the keratinocyte cell line, HaCaT. The steady-state level of specific acetylated nuclear proteins changed in a dynamic fashion in HaCaT cells induced with 1.2 mm calcium. One (approximately 97-kDa acetylated protein designated as ap97) was transiently induced, one (ap78) was induced and then continuously expressed, and one (ap70) disappeared with time. Although the up-regulation of ap70 and ap78 was not influenced by GF109203X, a specific inhibitor of protein kinase C (PKC), the calcium-induced accumulation of ap97 and the induction of P/CAF HAT activity were similarly attenuated by GF109203X. Notably, mutant P/CAF lacking HAT activity repressed the expression of ap97 and involucrin, a keratinocyte differentiation marker. Our results suggest that P/CAF HAT activity and induction of ap97 are involved in calcium-dependent keratinocyte differentiation.