Recurrence of Quadruple Extramammary Paget's Disease after 12 Years: A Case Report and Literature Review.

Introduction: Extramammary Paget's disease (EMPD) is a rare skin cancer that tends to be multicentric, with quadruple EMPD cases being scarcely reported. Case Presentation: We report the case of an 81-year-old man with heterochronous quadruple EMPD. Twelve years after total resection of vulvar EMPD, the patient developed erythematous lesions on the resection margin in the lower abdomen, umbilical region, and both axillae. Histological examination revealed that all lesions were in situ EMPD. Discussion: We reviewed six reported cases of quadruple EMPD with respect to race, sex, site, recurrence, time to recurrence, serum carcinoembryonic antigen, and depth. All patients were elderly Japanese males. In all but one case, the lesions were located in the apocrine region, which is a common site in such as the genital and axillary areas. Our case was the only heterochronous quadruple EMPD. The lesions were limited to the epidermis; therefore, they were unlikely to cause metastasis. It has been reported that the therapeutic effects of imiquimod can be expected in in situ EMPD. Therefore, quadruple EMPD may be a good indication of treatment option. Conclusion: EMPD is a disease whose pathogenesis is not yet clear; however, it is hoped that the origin and aetiology of EMPD will be elucidated from the clinical features of multiple EMPD in the future.

Evaluation of the antihistamine effects of olopatadine and levocetirizine during a 24-h period: a double-blind, randomized, cross-over, placebo-controlled comparison in skin responses induced by histamine iontophoresis.

The antihistamine effects of olopatadine and levocetirizine, in standard-dose application described in their information (5 mg twice a day for olopatadine; 5 mg once daily for levocetirizine), were examined from 11.5 to 24 h after application. The test was designed in a double-blind, randomized, cross-over, placebo-controlled study of 12 healthy volunteers on histamine-induced flare and wheal response using an iontophoresis technique. The suppressive effect of olopatadine on the wheals induced by a 0.1-mA histamine iontophoresis lasted for 24 h after dosing. Both drugs inhibited flare induced by histamine iontophoresis almost completely until 24 h after the first administration. Suppression of the 0.2-mA-induced wheal response by levocetirizine, taken once daily, decreased with time, although 0.1-mA-induced flare was almost completely suppressed by the drug. Olopatadine completely suppressed even the wheal response induced by a 0.2-mA histamine iontophoresis. Compared with the placebo, the two drugs significantly suppressed the subjective itching assessed by visual analog scale at all intervals. There were no significant differences in subjective drowsiness and objective cognitive function between drug- and placebo-treated subjects. These results demonstrate that olopatadine seems to be more potent than levocetirizine when administrated in a standard dose. In conclusion, mild to moderate urticaria could be controlled by standard application as described in their information. On the other hand, severe urticaria could be managed by a standard application of olopatadine, but levocetirizine may need an additional dose to control severe urticaria.

Thioredoxin upregulation by 5-aminolaevulinic acid-based photodynamic therapy in human skin squamous cell carcinoma cell line.

BACKGROUND/PURPOSE: 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT) is widely performed in the clinical setting for superficial skin cancers, giving favorable results, but residual tumor and recurrence occur occasionally. Thioredoxin is a common antioxidant that suppresses apoptosis and facilitates cell growth. We investigated the expression of thioredoxin following ALA-PDT in human skin squamous cell carcinoma cell line, HSC-5. METHODS: ALA-PDT was performed in HSC-5 cells using low-dose (5 J/cm(2), 100 mW/cm(2)) or high-dose (30 J/cm(2), 100 mW/cm(2)) irradiation, and the expression of thioredoxin was measured by Western blotting. An MTT assay was used to assess cell growth following a low dose of multiple irradiations. Cell death was examined by Western blotting for caspase-3 and PARP. Immunofluorescence double staining using annexin V and propidium iodine was also performed. RESULTS: Expression of thioredoxin was only observed following low-dose exposure ALA-PDT. Multiple low-dose exposure ALA-PDT significantly proliferated cell growth. With high-dose exposure ALA-PDT, caspase-3 and PARP expression were seen, and cell death due to apoptosis and/or necrosis was observed, but thioredoxin was barely detected. CONCLUSION: Low-dose exposure ALA-PDT increased the expression of thioredoxin and facilitated the growth of HSC-5 cells.

Differences in the effects of Na+-H+ exchange inhibitors on cardiac function and apoptosis in guinea-pig ischemia-reperfused hearts.

The protective effects of the Na+-H+ exchange (NHE) inhibitors SM-198110 (2-[[(aminoiminomethyl) amino] carbonyl]-4-chloro-1H-indole-1-propanesulfonic acid monohydrate) and SM-197378 (N-(aminoiminomethyl)-1-methyl-7-(sulfooxy)-4-(trifluoromethyl)-1H-indole-2-carboxamide monohydrate) were investigated in perfused Langendorff guinea-pig hearts subjected to ischemia (40 min) and reperfusion (40 min). The recovery of left ventricular developed pressure (LVDP) from ischemia by reperfusion was 39.0% in the control, while in the hearts pretreated with SM-198110 or SM-197378 (10(-7) M), it was about 100%. The ATP level, monitored simultaneously by (31)P-nuclear magnetic resonance spectrometry, was already higher than the control value at the end of the ischemic period, and the elevation in Na+ or Ca2+ fluorometric signals induced during ischemia was suppressed. In post-treated hearts, the LVDP recovery rate was significantly higher with SM-198110 than with SM-197378. By in vitro electron paramagnetic resonance spectrometry, SM-197378 was found to directly quench the active oxygen radical, whereas SM-198110 had no effect. Numbers of apoptotic cardiomyocytes after ischemia (1 h) followed by reperfusion (5 h) were significantly lower in SM-197378-treated than in SM-198110-treated hearts, consistent with the level of activity of caspase-3. These results suggest that the antioxidant effects of NHE inhibitors have an important role in apoptosis during ischemia-reperfusion, but apoptosis is not a major manifestation of cardiac function during postischemic recovery, and that NHE-sensitive mechanisms of reperfusion injury promote both necrotic and apoptotic processes death.

Primary lymphoma of the heart: case report and literature review.

Primary cardiac lymphoma (PCL) is a rare and usually fatal neoplasma. A case of PCL in a 78-year-old man who complained of exertional dyspnea and peripheral edema is presented. Echocardiography revealed a mass in the right atrium and a diagnosis of low-grade B-cell lymphoma was obtained with the surgically resected tumor. The lesion appeared to have originated in the right atrium and involved the right ventricle. The patient died of bronchopneumonia 8 months after the initial consultation. The present case and 39 patients with PCL reported between 1995 and 2002 were reviewed. Forty patients showed various and non-specific symptoms such as dyspnea, edema, arrhythmia and pericardial effusion. Primary cardiac lymphoma occurred slightly more often in male patients (M : F = 23:17) and in the elderly in general (mean age, 67 years), with lesions found in the following locations, listed in order of frequency: right atrium, pericardium, right ventricle, left atrium, left ventricle, and other sites. Antemortem diagnosis was obtained in 37 of the 40 patients. Thirty-seven cases were of B-cell lineage and two cases were of T-cell lineage. Complete remission was obtained in only 15 of the 40 patients. Although PCL antemortem diagnoses have been made in the majority of recent cases, the prognosis still remains poor.

The G12 family of heterotrimeric G proteins and Rho GTPase mediate Sonic hedgehog signalling.

Sonic hedgehog (Shh) is a secreted morphogen crucial for cell fate decision, cellular proliferation, and patterning during vertebrate development. The intracellular Shh signalling is transduced by Smoothened (Smo), a seven-transmembrane spanning protein that belongs to the G-protein coupled receptor family. Among four families of Galpha subunits, Galphai has been thought to be responsible for transducing Shh signalling, while several lines of evidence indicated that other signalling pathways may be involved. We found that the G12 family of heterotrimeric G proteins and the small GTPase RhoA are involved in Shh/Smo-mediated cellular responses, including stimulation of target gene promoter and inhibition of neurite outgrowth of neuroblastoma cells. We also found that the G12/RhoA pathway is responsible for Smo-induced nuclear import of GLI3 which is thought to transduce Shh signals to nucleus. Furthermore, misexpression of a G12-specific GTPase-activating protein in rat neural tubes leads to pertubation of motor neurone and interneurone development, mimicking the effects of decreased Shh signalling. These results show that Shh signalling is mediated in part by activating G12 family coupled signalling pathways. The participation of RhoA, a pivotal molecular switch in many signal transduction pathways, may help explain how Shh can trigger a variety of cellular responses.

A role of activated Sonic hedgehog signaling for the cellular proliferation of oral squamous cell carcinoma cell line.

Sonic hedgehog (Shh) is a secreted morphogen crucial for appropriate cellular proliferation during mammalian development. The activated Shh signaling is known to predispose to human tumors such as medulloblastoma and basal cell carcinoma, while a role of Shh signaling in the other common tumors is still controversial. Here we showed the overexpression of Shh in five cell lines among 14 human oral squamous cell carcinoma (OSCC) cell lines. One of the Shh-expressing OSCC cell lines HSQ-89 showed the inhibition of G1/S transition and apoptotic cell death by treatment with Cyclopamine, a steroidal alkaloid that blocks the intracellular Shh signaling. Furthermore, we found that treatment with Y-27632, a specific inhibitor of Rho-associated kinase, mimicked the effect of Cyclopamine on the cell cycle progression of HSQ-89. Our study revealed the involvement of activated Shh signaling in the cellular proliferation of OSCC cells, indicating Shh signaling might be a good therapeutic target for OSCC.

Diversity of restitution after deoxycholic acid-induced small intestinal mucosal injury in the rat.

Repair of superficial damage to gastrointestinal mucosa occurs by a process called restitution, with epithelial integrity and continuity reestablished before cell proliferation occurs. The aim of the present study was to investigate the diversity of restitution in rat jejunum exposed to different concentrations of deoxycholic acid (DOC; 1.5-100 mmol/liter). Following a 30-min exposure, the intestine was allowed to recover for 15-330 minutes. DOC caused dose-dependent tissue destruction. Exfoliating epithelial cells were already observed after 5 min of exposure (1.5 mmol/liter), with simple sloughing off and resealing of the tips. Moderately affected epithelium (20 mmol/liter) demonstrated denudation of villous tips and then became covered with goblet cells. Severely affected epithelium (100 mmol/liter) also appeared to be replaced with goblet cells. These data suggest that the reversibility of mucosal damage induced by DOC is due to a variety of processes, which depend on the severity of the mucosal insult.

Rat small intestinal goblet cell kinetics in the process of restitution of surface epithelium subjected to ischemia-reperfusion injury.

Repair of superficial damage to gastrointestinal mucosa occurs by a process called restitution. Goblet cells reside throughout the length of the intestine and are responsible for the production of mucus. However, a kinetic analysis of goblet cell dynamics of small intestine in restitution has hitherto not been reported. The aim of the present study was to investigate the role of goblet cells in the process of restitution of rat small intestine subjected to ischemia and ischemia-reperfusion injury, and therefore intestinal epithelium from rats subjected to both ischemia and ischemia-reperfusion was studied. Detachment of enterocytes was observed after 5-min of reperfusion. After 20-30 minutes of reperfusion, the denuded villous tips were covered with goblet cells. Within 75 min of reperfusion the epithelium restitution was complete. On the other hand, restitution was not observed in ischemia group. These data suggest that goblet cells may play an important role in restitution after ischemia-reperfusion injury.