Discoid lupus erythematosus exacerbated by contact dermatitis caused by use of squaric acid dibutylester for topical immunotherapy in a patient with alopecia areata

A 57-year-old Japanese male patient with an 18-year history of discoid lupus erythematosus (DLE) presented with alopecia on his scalp, and was clinically diagnosed to have alopecia areata. He was started on topical immunotherapy with squaric acid dibutylester (SADBE) for the treatment of alopecia areata. The patient was first sensitized with the application of 2% SADBE on the right upper arm, followed subsequently by re-exposure to a low concentration of SADBE to provoke contact dermatitis on the scalp as treatment. Approximately 2 months later, he developed multiple red scaly lesions on his scalp and face, which were diagnosed histopathologically as DLE. DLE is known to be exacerbated by a variety of factors, including sunlight, X-rays, tattoos, burns, and some forms of cutaneous trauma, including dermatitis. However, to the best of our knowledge, there have only been two reported cases of DLE exacerbated by contact dermatitis.     

By inhibiting Src,verapamil and dasatinib overcome multidrug resistance via increased expression of Bim and decreased expressions of MDR1 and survivin in human multidrug-resistant myeloma cells

The calcium channel blocker verapamil inhibits the transport function of multidrug resistance protein 1 (MDR1). Although verapamil acts to reverse MDR in cancer cells, the underlying mechanism remains unclear. In the present study, we investigated the mechanism of reversing MDR by verapamil in anti-cancer drug-resistant multiple myeloma (MM) cell lines. We found that verapamil suppresses MDR1 and survivin expressions and increases Bim expression via suppression of Src activation. Furthermore, dasatinib reversed the drug-resistance of the drug-resistant cell lines. These findings suggest that Src inhibitors are potentially useful as an anti-MDR agent for the treatment of malignant tumor cells.     

Scavenger receptors for oxidized lipoprotein in age-related macular degeneration

PURPOSE: The accumulation of macrophages is known to be involved in the pathogenesis of age-related macular degeneration (AMD), but the reasons why macrophages accumulate in AMD lesions have not been determined. Because the histopathology of AMD has some factors common with those of atherosclerosis, the authors hypothesized that macrophages accumulate to take up oxidized lipoproteins in the eyes of patients with AMD, as has been demonstrated in atherosclerosis. METHODS: Immunohistochemistry was performed on 10 surgically excised choroidal neovascular (CNV) membranes from eyes with AMD. An antibody against oxidized lipoprotein and antibodies against the scavenger receptors SR-PSOX and LOX-1 were used. Antibodies against cytokeratin, CD68, and von Willebrand factor were used to identify retinal pigment epithelium (RPE), macrophages, and vascular endothelial cells, respectively. RT-PCR was performed to detect the mRNAs of the scavenger receptors in the CNV membranes. RESULTS: Oxidized lipoproteins were immunohistochemically detected in the CNV membranes. Intense immunostaining was observed at the surface of the CNV membranes with the SR-PSOX antibody, whereas LOX-1 immunostaining was weak. Cells expressing scavenger receptors were found to be predominantly macrophages with a minority of RPE. Both SR-PSOX and LOX-1 mRNAs were detected in CNV membranes. CONCLUSIONS: Oxidized lipoproteins are present in AMD lesions. Macrophages and RPE in the CNV membranes express cell surface scavenger receptors for oxidized lipoproteins. These findings suggest that macrophages may accumulate to take up oxidized lipoproteins in AMD and that the control of oxidative stress and macrophage responses may therefore be potential treatments for AMD.     

A comparative study of physical work load in Japanese and Swedish nursery school teachers

Comparisons were made of general and local physical work loads between two groups of 58 Japanese and 15 Swedish nursery school teachers. Heart rate, number of steps, rating of perceived exertion (RPE), frequency and time expended with respect to trunk flexion, sitting/kneeling, and lifting/carrying loads of 1?kg or more were monitored during working hours. The average percentage heart rate increase in the maximal heart rate range was lower in the Japanese than in the Swedish teachers. However, all parameters of local physical work load indicating musculoskeletal stress were higher in the Japanese than in the Swedish teachers. The RPE was slightly higher in the Japanese than in the Swedish teachers. These features of general and local work load in the Japanese teachers were typically observed among the teachers in charge of very young children (0–2?years). The Japanese teachers in charge of children aged 3–5 years, on the other hand, had similar levels of both general and local work load as the Swedish teachers in charge of classes comprising children of various ages (1–5?years). The physical work load measured in the present study was not sufficient to explain the difference in the magnitude of musculoskeletal problems for nursery school teachers in the two countries, and other factors should now be examined.     

The action of a novel vitamin D3 analogue, OCT, on immunomodulatory function of keratinocytes and lymphocytes

Abstract Topical vitamin D₃ has relatively recently been introduced for the treatment of psoriasis. Synthetic vitamin D₃ analogues with a high potential for inducing differentiation of cells, but with a low hypercalcemic effect have recently been developed. One such synthetic analogue of 1,25-dihydroxyvitamin D₃ (calcitriol), 22-oxacalcitriol (OCT), is a novel agent for the topical treatment of psoriasis. The activity of OCT in vitro was investigated and compared with that of a series of vitamin D₃ analogues as to their ability to inhibit murine T lymphocyte proliferation stimulated by con-A, to suppress IL-6 and IL-8 production by keratinocytes stimulated with IL-1α and TNFα, and to inhibit AP-1- and NFκB-dependent reporter gene expression. OCT inhibited the proliferation of lymphocytes and suppressed IL-8 and IL-6 production by keratinocytes to the same extent as the other vitamin D₃ analogues. It also inhibited AP-1- and NFκB-controlled luciferase activity to the same extent as the other vitamin D₃ analogues, which demonstrates its mechanism of action in the suppression of inflammatory processes. Received: 26 January 1999 / Received after revision: 10 June 1999 / Accepted: 11 June 1999     

Signet-ring cell carcinoma of the colon 7mm in size with peritonitis carcinomatosa

Received: November 24, 2000 / Accepted: April 27, 2001     

Circadian secretion patterns of melatonin after major surgery

Abstract: Biorhythms, such as regular variation in core body temperature and the pattern of the secretion of melatonin, are thought to be mediated by the same biological clock. Core body temperature is affected by the inflammatory response to major surgery. Apart from the well-known inhibitory effect of bright light on its secretion, melatonin is an exceedingly good marker of one of the central generating systems of circadian rhythms. We sequentially measured the plasma melatonin concentration pattern in patients who had undergone esophagectomy with thoracotomy to elucidate the circadian rhythm after major surgery. From seven patients who had received esophagectomy with thoracotomy for esophageal cancer, plasma concentrations of melatonin were measured using an RIA method. Blood samples were collected via each patient's arterial line at 00.00, 02.00, 04.00, 06.00, 08.00, 12.00, 16.00, 20.00, and 24.00 hr on the first postoperative day for six of the patients, and, for one patient, every 2 hr until the third postoperative day and every 4 hr thereafter until the sixth postoperative day. Four patients out of seven had melatonin concentrations of over 30 pg/ml (mean 34 pg/ml) at 24.00 hr on the first postoperative day. Five patients showed circadian secretion patterns of melatonin during the first postoperative day. One patient whose melatonin concentrations were measured consecutively for 6 days showed a regular circadian secretion pattern through the 6 days of the study. Even the stress caused by extremely invasive surgery did not significantly disturb the melatonin secretion pattern.