The relationship between clinical characteristics including presence of exposed lesions and health-related quality of life (HRQoL) in patients with psoriasis: analysis from the nationwide epidemiologic study for psoriasis in Korea (EPI-PSODE study).

BACKGROUND: Psychological aspect and quality of life should be considered in treating patients with psoriasis. OBJECTIVE: We sought to ascertain which clinical characteristics including presence of exposed lesions are associated with impairment of health-related quality of life (HRQoL) in patients with psoriasis. METHODS: The EPI-PSODE study was a nationwide, multicenter, cross-sectional study conducted in Korea that included 1260 adult patients with psoriasis. In addition to clinical characteristics including presence of exposed lesions, data were collected using the Psoriatic Arthritis (PsA) Screening and Evaluation (PASE), Dermatology Life Quality Index (DLQI), MOS 36-Item Short-Form Health Survey (SF-36), Work Productivity and Activity Impairment Questionnaire Psoriasis (WPAI: PSO) and Medication Satisfaction Questionnaire (MSQ). RESULTS: Patients with a DLQI score > 5 (n = 990) were younger, had an earlier onset of psoriasis, scored higher on the Psoriasis Area and Severity Index (PASI), had higher body surface area (BSA) and had higher PASE scores than patients with DLQI ≤ 5 (n = 266). The group of patients with exposed lesions (n = 871) were younger and male predominance, earlier onset of psoriasis, longer disease duration, higher PASI/BSA score and a higher proportion with drinking and smoking history each than the group of patients without exposed lesions (n = 389). Presence of exposed lesions negatively influenced DLQI, 36-Item Short-Form Health Survey (SF-36) (mental component), presenteeism, total work productivity impairment and total activity impairment in the WPAI: PSO. In multiple regression model, PASI score was the only variable which was significantly associated with all HRQoL measures. Presence of exposed lesions was a significant factor affecting DLQI and SF-36 (mental). CONCLUSION: The presence of exposed lesions has a negative impact on quality of life, mental health and work productivity. Therefore, effective treatments are particularly needed for psoriasis patients with exposed lesions.

A comparative split-face study of photodynamic therapy with indocyanine green and indole-3-acetic acid for the treatment of acne vulgaris.

BACKGROUND: Recently, photodynamic therapy (PDT) using a variety of light sources and photosensitizers has been used for the treatment of acne vulgaris. PDT with aminolaevulinic or methylaminolaevulinic acid has also been used in clinical trials as a treatment for acne, but adverse effects such as pain, erythema and pustular eruption are common. Indocyanine green (ICG) and indole-3-acetic acid (IAA), newer photosensitizers, are known to have minimal adverse effects. OBJECTIVES: This study was designed to compare the safety and efficacy of PDT using ICG and PDT using IAA in the treatment of mild to moderate acne vulgaris. METHODS: In this prospective, single-blind, clinical trial, 34 patients with mild to moderate acne were treated with IAA with green light (520 nm) on half of the face and with ICG with near-infrared radiation (805 nm) on the other half. The procedure was carried out five times at 1-week intervals. RESULTS: With regard to acne lesions (inflammatory and noninflammatory) and sebum secretion, there were statistically significant reductions at each time point compared with the baseline values (P < 0·05). However, there were no statistically significant differences between the two treatment types (P > 0·05). Both ICG-PDT and IAA-PDT showed better responses for inflammatory lesions than for noninflammatory lesions (P < 0·05). Subjective satisfaction score were statistically significant at 4 and 5 weeks of treatment as well as at 1, 2 and 3 months follow-up (P < 0·05). CONCLUSIONS: Both PDT with ICG and PDT with IAA are safe and effective for the treatment of mild to moderate acne vulgaris.

Down-regulation of TGF-beta and VCAM-1 is associated with successful treatment of chronic rejection in rats.

We measured the expression levels of transforming growth factor-beta (TGF-beta) and vascular cell adhesion molecule (VCAM-1) in rat kidney grafts undergoing chronic rejection and treated the rats with six different regimens in order to determine correlation between their expression levels and severity of chronic rejection. F344 or Lewis kidneys were transplanted into Lewis recipients to generate allograft or isograft groups, respectively. Graft recipients were treated with one of the following regimens: (1) untreated isograft, (2) untreated allograft, (3) tacrolimus (FK506), 1 mg/kg/d for 10 days, (4) triptolide (PG490-88), 0.5 mg/kg/d for 10 days, and (5) leflunomide analogue (FK778), 10 mg/kg/d for 10 days. Kidneys were harvested on day 90 after transplantation and subjected to histological analysis and gene expression analysis by real-time reverse transcriptase polymerase chain reaction (RT-PCR) for TGF-beta and VCAM-1. Gene expression values were compared to measurements of chronic rejection by linear regression analysis. Modified Banff score for transplant pathology show that chronic rejection was mild in the FK778 group, moderate in the PG490-88 group, and severe in the FK506 and allograft control groups. Overall, the expression levels of TGF-beta and VCAM-1 show high correlations with histological changes of chronic rejection. Suppression of the expression levels of TGF-beta and VCAM-1 is associated with the amelioration of chronic rejection by various drugs, suggesting that these molecules are important key molecules in chronic rejection.

Protective effects of PG490-88 on chronic allograft rejection by changing intragraft gene expression profiles.

Our previous study showed that PG490-88 effectively ameliorated both functional and histological changes of chronic rejection in the rat. In this experiment, we investigated the intragraft gene expression profiles of PG490-88 under successful prevention of chronic rejection in rat kidney allografts. Kidneys of F344 rats were transplanted into bilaterally nephrectomized LEW recipients. Recipients with a brief course of low-dose FK506 (1 mg/kg per day for 10 days) were dosed with PG490-88 0.5 mg/kg per day, which was predetermined and defined as the effective dose of preventing chronic allograft rejection in this model, for 90 days after grafting. Kidney grafts were harvested on day 90 after transplantation and subjected to gene expression analysis by real-time RT-PCR. Overall, the expression levels of all genes tested were upregulated in the brief course of low-dose FK506 control. PG490-88 treatment exhibited significant inhibition of intragraft m RNA levels of iNOS, IL-6, and perforin and marginal downregulation of IL-2, IFNgamma, IRF-1, TNFalpha, and TGFbeta. There was no change in IL-10, granzyme B, and PDGFalpha, when compared to the brief course of low-dose FK506 control. These results suggested that downregulation of multiple intragraft gene expression by mainly suppression of iNOS, IL-6, and perforin might be responsible for successful prevention of chronic kidney allograft nephropathy by PG490-88 in rats.

PG490-88, a new immunosuppressant, effectively prevents acute and chronic rejection in rat renal allografts.

PG490-88 is a semisynthetic derivative of the novel compound PG490 (triptolide) purified from a Chinese herb. It has been shown to prolong acute allograft survival in multiple experimental organ transplant models. However, the effect of PG490-88 on prevention of acute and chronic renal allograft rejection has not been determined. Kidneys of ACI or F344 rats were transplanted into bilaterally nephrectomized LEW recipients as the acute or chronic allograft rejection models, respectively. Treatment of LEW recipients with PG490-88 significantly prolonged ACI kidney graft survival in a dose-dependent manner when compared with the untreated allograft controls. LEW recipients of F344 kidney grafts who received PG490-88 for 90 days with a brief course of low-dose FK506 showed normal serum creatinine levels and markedly reduced histological changes of chronic rejection at day 90 after transplantation. These results suggest that PG490-88 significantly prolongs kidney allograft survival in an acute rejection model and prevents chronic allograft rejection in rats.

Notch signaling as a target in multimodality cancer therapy.

Notch signaling is an extremely conserved and widely used mechanism controlling cell fate determination. Recent evidence shows that Notch receptors regulate cell differentiation, proliferation and apoptosis in many cells, including neoplastic cells. In the context of cancer experimental immunotherapy and multimodality therapy, the Notch signaling network is acquiring increasing importance for its possible roles in both neoplastic cells and the immune system. In this review, we discuss: (i) the roles of Notch signaling in cancer cells and the immune system; and (ii) strategies through which Notch-targeting biologicals may be used to increase the effectiveness of multimodality cancer treatment, including cancer vaccines.

Epithelioid leiomyosarcoma of the skin.

We report a case of epithelioid leiomyosarcoma that developed on the nose of a 55-year-old Korean male over a one year period. The lesion was a pea sized, firm, erythematous, painless nodule with erosion in the center. Histologic examination revealed short spindled cells with blunt-ended nuclei and pleomorphic round to oval epithelioid cells with abundant eosinophilic cytoplasm that were perivascular and densely packed in the dermis. Immunostaining for desmin was negative, although stains for vimentin and smooth muscle actin were both strongly positive.

Cryopreservation of Taxus chinensis suspension cell cultures.

A simple cryopreservation method for suspension cells of Taxus chinensis was established. In this procedure 7 days old suspension cells were used without any pre-culture treatment. At first, cells were incubated in cryoprotectant solution (0.5M DMSO and 0.5M glycerol) on ice for 30 min and then frozen at a cooling rate of 1 degree C/min to -40 degrees C prior to immersion in liquid nitrogen. The average viability of frozen-thawed cells was between 30 to 40%. The recovery of cryopreserved cells in liquid nitrogen for 1 month was accomplished. After rapid thawing, cells were transferred to solid medium and cultivated for 4-6 weeks. The treatment of trehalose as a cryoprotectant enhanced re-growth of frozen-thawed cells. The stable maintenance of paclitaxel biosynthetic ability in cryopreserved cells was confirmed by comparing with that of regularly sub-cultured suspension cells.

Treatment of landfill leachate by a pilot-scale modified Ludzack-Ettinger and sulfur-utilizing denitrification process.

Nitrogen removal efficiency of a pilot-scale system consisted of Modified Ludzack-Ettinger (MLE) followed by sulfur-utilizing denitrification (SUDNR) process was evaluated with a landfill leachate. For SUDNR, a down-flow mode sulfur packed bed reactor (SPBR) filled with sulfur and limestone particles was used. Although total nitrogen removal efficiency of the MLE process was about 80% at the recycle ratio of 4, effluent contained 350-450 mg/L NO(3-)-N. Up to a loading rate of 1.2 kg NO(3-)-N/m3-day, the SPBR could achieve complete removal of nitrate, and nitrate removal rate was kept to that level even at higher loading rate. When a COD/N ratio of MLE process was maintained at 2 instead of 4, more organics with molecular weight less than 500 were utilized for heterotrophic denitrification although denitrification was not complete with the lack of electron donors. Clogging in the SPBR, mainly by the accumulation of nitrogen gas in the pores, could easily be removed by introducing the effluent in an upward direction for 1 min at 1 hr intervals. The proposed treatment system could achieve nitrate free effluent with a slight increase in chemical cost. Furthermore, depending on further COD removal requirement after biological treatment, the proposed treatment system can be an economical solution.

Is asymptomatic hemorrhagic transformation really innocuous?

OBJECTIVES: Asymptomatic hemorrhagic transformation (HT) is not associated with immediate deterioration of patients with acute ischemic stroke. However, it is unclear whether it is clinically innocuous with respect to long-term outcome. The aim of this study was to determine the impact of asymptomatic HT on 3-month outcome. METHODS: A consecutive series of 1,618 patients, hospitalized between January 2004 and August 2007 for ischemic stroke within 7 days from symptom onset were identified in a prospective stroke registry database. Those who had no evidence of acute cerebral ischemia on diffusion-weighted MRI, who did not undergo T2-weighted gradient echo MRI, whose modified Rankin Scale (mRS) score at 3 months after stroke onset was not available, or who had symptomatic HT were excluded. The odds ratio (OR) of asymptomatic HT was calculated for the full distribution of mRS score and adjusted for variables with p < 0.25 with respect to their associations with asymptomatic HT or functional outcome. RESULTS: Of 1,412 patients eligible for the study, 100 (7.1%) had asymptomatic HT. Patients who experienced asymptomatic HT were more likely to have cardioembolic stroke, to receive thrombolytic therapy, to receive anticoagulation with heparin, and to have a higher initial NIH Stroke Scale score. The crude and adjusted ORs of asymptomatic HT for an increment of mRS score at 3 months were 2.94 (95% confidence interval 2.05-4.24) and 1.90 (1.27-2.82), respectively. CONCLUSIONS: Our study shows that the odds of a worse outcome are increased by a factor of 2 in patients with asymptomatic HT compared with those without HT after acute ischemic stroke.

Phosphorylation by polo-like kinase 1 induces the tumor-suppressing activity of FADD.

Phosphorylation of the Fas-associated death domain (FADD) protein sensitizes cancer cells to various chemotherapeutics. However, the molecular mechanism underlying chemosensitization by phosphorylated FADD (P-FADD) is poorly understood. In this study, we describe the physical interactions and functional interplay between Polo-like kinase 1 (Plk1) and FADD. Plk1 phosphorylates FADD at Ser-194 in response to treatment with taxol. Overexpression of a phosphorylation-mimicking mutant, FADD S194D, caused degradation of Plk1 in an ubiquitin-independent manner, and delayed cytokinesis, consistent with the expected cellular phenotype of Plk1 deficiency. This demonstrates that Plk1 is regulated via a negative feedback loop by its substrate, FADD. Overexpression of FADD S194D sensitized HeLa cells to a low dose of taxol independently of caspase activation, whereas overexpression of FADD S194D resulted in caspase activation in response to a high dose of taxol. Therefore, we examined whether the death potential of P-FADD affected Plk1-mediated tumorigenesis. Transfection of FADD S194D inhibited colony formation by Plk1-overexpressing HeLa cells (HeLa-Plk1). Moreover, overexpression of FADD S194D suppressed tumorigenesis in nude mice xenografted with HeLa-Plk1. Therefore, this study reports the first in vivo validation of tumor-suppressing activity of P-FADD. Collectively, our data demonstrate that in response to taxol, Plk1 endows death-promoting and tumor-suppressor functions to its substrate, FADD.

Transforming growth factor-beta1 regulates the fate of cultured spinal cord-derived neural progenitor cells.

OBJECTIVES: We have evaluated the physiological roles of transforming growth factor-beta1 (TGF-beta1) on differentiation, migration, proliferation and anti-apoptosis characteristics of cultured spinal cord-derived neural progenitor cells. METHODS: We have used neural progenitor cells that had been isolated and cultured from mouse spinal cord tissue, and we also assessed the relevant reaction mechanisms using an activin-like kinase (ALK)-specific inhibitory system including an inhibitory RNA, and found that it involved potential signalling molecules such as phosphatidylinositol-3-OH kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK1/2). RESULTS AND CONCLUSIONS: Transforming growth factor-beta1-mediated cell population growth was activated after treatment and was also effectively blocked by an ALK41517-synthetic inhibitor (4-(5-benzo(1,3) dioxol-5-yl-4-pyridine-2-yl-1H-imidazole-2-yl) benzamide (SB431542) and ALK siRNA, thereby indicating the involvement of SMAD2 in the TGF-beta1-mediated growth and migration of these neural progenitors cells (NPC). In the present study, TGF-beta1 actively induced NPC migration in vitro. Furthermore, TGF-beta1 demonstrated extreme anti-apoptotic behaviour against hydrogen peroxide-mediated apoptotic cell death. At low dosages, TGF-beta1 enhanced (by approximately 76%) cell survival against hydrogen peroxide treatment via inactivation of caspase-3 and -9. TGF-beta1-treated NPCs down-regulated Bax expression and cytochrome c release; in addition, the cells showed up-regulated Bcl-2 and thioredoxin reductase 1. They also had increased p38, Akt and ERK1/2 phosphorylation, showing the involvement of both the PI3K/Akt and MAPK/ERK1/2 pathways in the neuroprotective effects of TGF-beta1. Interestingly, these effects operate on specific subtypes of cells, including neurones, neural progenitor cells and astrocytes in cultured spinal cord tissue-derived cells. Lesion sites of spinal cord-overexpressing TGF-beta1-mediated prevention of cell death, cell growth and migration enhancement activity have been introduced as a possible new basis for therapeutic strategy in treatment of neurodegenerative disorders, including spinal cord injuries.

Narrowbore high-performance liquid chromatography for the simultaneous determination of sildenafil and its metabolite UK-103,320 in human plasma using column switching.

A fully automated narrowbore high-performance liquid chromatography method with column switching was developed for the simultaneous determination of sildenafil and its active metabolite UK-103,320 in human plasma samples without pre-purification. Diluted plasma sample (100 microl) was directly introduced onto a Capcell Pak MF Ph-1 column (20x4 mm I.D.) where primary separation occurred to remove proteins and concentrate target substances using 15% acetonitrile in 20 mM phosphate solution (pH 7). The drug molecules eluted from the MF Ph-1 column were focused in an intermediate column (35x2 mm I.D.) by a valve switching step. The substances enriched in the intermediate column were eluted and separated on a phenyl-hexyl column (100x2 mm I.D.) using 36% acetonitrile in 10 mM phosphate solution (pH 4.5) when the valve status was switched back. The method showed excellent sensitivity (detection limit of 10 ng/ml), good precision (RSD < or = 2.3%) and accuracy (bias: +/-2.0%) and speed (total analysis time 17 min). The response was linear (r2 > or = 0.999) over the concentration range 10-1000 ng/ml.

Clinicopathological and genotypic aspects of anticonvulsant-induced pseudolymphoma syndrome.

BACKGROUND: Pseudolymphoma syndrome (PLS) is relatively rare but can lead to death if there are extensive skin lesions, severe hepatitis, agranulocytosis and neutropenia. PLS may also give rise to harmful effects if misdiagnosed as malignant lymphoma and patients with PLS are treated unnecessarily with chemotherapy, because it may mimic histologically other lymphomas, including mycosis fungoides (MF). OBJECTIVES: To examine the clinicopathological and genotypic features of anticonvulsant-induced PLS. Patients and methods We retrospectively reviewed clinical, laboratory and histological findings for eight cases of anticonvulsant-induced PLS, and performed T-cell receptor gene rearrangement using polymerase chain reaction with paraffin-embedded specimens from each case. RESULTS: The causative agents were carbamazepine (four cases), phenytoin (two cases), phenobarbital (one case) and valproic acid (one case). A cross-reaction between phenobarbital and phenytoin was observed in one case. The duration from the start of anticonvulsant therapy to skin eruption was 3-24 weeks (mean 7 weeks). The skin lesions were generalized maculopapular eruptions in all cases, including one case accompanied by vesiculopustular lesions. The frequencies of the associated features were as follows: facial oedema (88%), fever (75%), lymphadenopathy (63%), and hepatomegaly (25%). Laboratory findings revealed leukocytosis, atypical lymphocytes, eosinophilia, monocytosis, neutrophilia, lymphocytosis and abnormal liver function. Histopathologically, there was similarity between PLS and MF in that epidermotrophism of atypical lymphocytes (100%) and Pautrier's microabscess-like structures (38%) were observed. However, PLS has some differences from MF that include moderate to marked spongiosis (75%), necrotic keratinocytes (63%), and infiltration of eosinophils (25%) in the epidermis and, in the dermis, papillary dermal oedema (100%), extravasated erythrocytes (100%), lymphocytes within the dermis larger than those within the epidermis (63%), and infiltration of various inflammatory cells including neutrophils (50%). Genotypic analysis demonstrated a rearrangement of the T-cell receptor-gamma gene in one of eight cases studied. There were no deaths and all cases were improved at 2-9 weeks (mean 6 weeks), after the cessation of causative agents, systemic and topical corticosteroid therapy, and symptomatic therapy. There were no significant differences in clinical, laboratory and histological findings between the causative agents. CONCLUSIONS: PLS may show histopathological findings similar to MF and take a prolonged course even after the cessation of causative agents. Thus, a clear understanding and diagnosis of this disease is considered to have an important effect on treatment and prognosis.

Mycosis fungoides presenting as Ofuji's papuloerythroderma.

We report three patients presented with clinical features of Ofuji's papuloerythroderma (pruritic erythematous papules and extensive erythema sparing all skin folds), however, showing histopathological findings of mycosis fungoides (Pautrier's microabscess, haloed lymphocytes, disproportionate epidermotropism, and wiry collagen bundles). One case was associated with plaque stage of mycosis fungoides and follicular mucinosis. T-cell receptor (TCR) gene rearrangement analysis in the lesional skin tissue demonstrated rearrangement of the gamma chain in all cases. HTLV-1 serology was negative for two patients who conducted HTLV-1 test. We think that Ofuji's papuloerythroderma might be a variant of early mycosis fungoides rather than secondary skin manifestations to certain cutaneous inflammatory diseases.

Mycosis fungoides mimicking inflammatory linear verrucous epidermal nevus.

We experienced an unusual case of mycosis fungoides with the clinical and histological features mimicking inflammatory linear verrucous epidermal nevus (ILVEN) in an 11-year-old boy. Localized linear multiple pruritic verrucous confluent papules and plaques appeared on the his left elbow, forearm and hand for 7 months. Skin biopsies showed characteristic findings of mycosis fungoides (e.g. Pautrier's microabscesses, follicular epitheliotropism, wiry bundles of collagen, etc.). T-cell receptor gene rearrangement analysis in the lesional skin demonstrated rearrangement of the gamma chain. RePUVA (systemic PUVA with retinoic acid) therapy improved his skin lesions and pruritus, but these progressed after discontinuation of treatment. Thus, lesions mimicking ILVEN can be an unusual and potentially misleading presentation of mycosis fungoides.

Evaluation of selected lichens from iceland for cancer chemopreventive and cytotoxic activity.

Cancer chemopreventive effects of organic extracts from 29 species of lichens collected in Iceland were evaluated using a panel of in vitro bioassays whereby extracts were tested for potential to induce quinone reductase (QR) and differentiation of human promyelocytic leukemia (HL-60) cells, inhibit cyclooxygenase-1 (COX-1), phorbol ester-induced ornithine decarboxylase (ODC), aromatase and sulfatase, as well as for antioxidant, estrogenic/anti-estrogenic and antiproliferative activity. In addition, the extracts were tested for cytotoxicity against 12 cancer cell lines. The most significant results were exhibited by extracts from Xanthoria elegans and Alectoria nigricans , which respectively, induced QR activity (concentration to double activity = 4.8 µg/ml) and inhibited phorbol ester-induced ODC activity with mouse 308 cells in culture (IC 50 = 2.6 µg/ml). Moderate inhibition of [ 3 H]thymidine incorporation with HL-60 cells was exhibited by the Peltigera leucophlebia extract. Several extracts prevented estrogen formation from estrogen precursors by inhibiting the enzymatic activities of aromatase ( Sphaerophorus globosus , Cetrariella delisei , Melanelia hepatizon ) and sulfatase ( Cladonia gracilis , Sphaerophorus fragilis , S. globosus ). None of the extracts demonstrated significant cytotoxic effects with selected cell lines.