Edaravone (MCI-186) is effective as a free radical scavenger following arteriovenous sheathotomy for treatment of macular oedema associated with branch retinal vein occlusion.

AIMS: To determine whether edaravone (MCI-186), a free radical scavenger, can reduce macular oedema and improve the visual acuity after arteriovenous sheathotomy in eyes with a branch retinal vein occlusion (BRVO). METHODS: Forty-seven eyes of 47 consecutive patients with a BRVO who were treated with arteriovenous sheathotomy were studied. The patients were assigned prospectively to either Group R who received 30 mg of edaravone (Radicut) systemically during the vitrectomy or Group N who did not receive any drugs. The postoperative visual acuity was measured before and 12 months after the operation. RESULTS: At 12 months postoperatively, the best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution (logMAR) units improved significantly from 0.22 to 0.56 logMAR units in Group R and from 0.20 to 0.27 units in Group N (p = 0.016). Twenty-three of 27 cases (85%) in Group R and four of 15 cases (27%) in Group N showed an improvement in BCVA of >0.2 logMAR units (p = 0.0025). CONCLUSION: The better visual acuity in patients given edaravone than those without endaravone during the arteriovenous sheathotomy suggests that edaravone improved the physiology of the retinal cells after the arteriovenous sheathotomy.

Granulomatous mycosis fungoides presenting as poikiloderma.

Granulomatous mycosis fungoides (MF) is a rare subtype of MF, characterized by the histological presence of a granulomatous reaction, but distinct clinical characteristics are not present. A 41-year-old healthy man presented with poikiloderma, ichthyosis and erythematous scaly plaque. Histological examination of a biopsy taken from poikilodermic skin showed a granulomatous reaction to epidermotropic atypical lymphocytes. However, in other areas there were only findings of conventional MF without granuloma. Granulomatous MF may be associated with poikiloderma.

Increased expression of HLA-DR and CD86 in nasal epithelial cells in allergic rhinitics: antigen presentation to T cells and up-regulation by diesel exhaust particles.

BACKGROUND: A proportion of nasal epithelial cells (NEC) in patients with allergic rhinitis (AR) are known to express the major histocompatibility complex Class II molecule (HLA-DR). OBJECTIVE: We hypothesized that NEC may play a role in antigen presentation to T cells. To elucidate the possible role of NEC in antigen presentation, we examined the expression of HLA-DR, CD80 and CD86 in NEC, their regulation by cytokines and the capacity of NEC to induce antigen-specific proliferation of T cells. METHODS: We examined the expression of HLA-DR, CD80 and CD86 in nasal epithelial scrapings of patients with seasonal allergic rhinitis (SAR) to Japanese cedar pollen pre-season and in-season, by immunohistochemistry. Next, we examined the effect of IL-1beta, TNF-alpha, (IFN-gamma), IL-4 alpha, IL-13 and diesel exhaust particles (DEP) on the HLA-DR, CD80 and CD86 expression in cultured nasal epithelial cells (CNEC), by flow cytometry. Further, we analysed the capacity of mite antigen (Der f II)-pulsed mitomycin-C-treated CNEC to induce proliferation of autologous T cells from patients with perennial allergic rhinitis. RESULTS: NEC constitutively expressed HLA-DR and CD86, but not CD80. The expression of HLA-DR and CD86 in NEC was significantly increased in-season, in patients with SAR as compared with that of pre-season. While IFN-gamma up-regulated the expression of HLA-DR, IL-1beta and TNF-alpha up-regulated the expression of CD86 in CNEC. Furthermore, in the presence of mite antigen, CNEC induced the proliferation of autologous peripheral blood T lymphocytes. Anti-CD86 and anti-HLA-DR monoclonal antibody but not anti-CD80 inhibited the epithelial cell-induced T cell proliferation. Stimulation with a combination of DEP and mite antigen significantly up-regulated HLA-DR and CD86 expression in CNEC. CONCLUSIONS: These studies suggest that NEC in patients with AR may play a role in antigen presentation through the enhanced expression of HLA-DR and CD86. Furthermore, these results suggest the possibility that DEP may enhance the antigen-presenting function of CNEC.

The effect of dexamethasone on defective nephrin transport caused by ER stress: a potential mechanism for the therapeutic action of glucocorticoids in the acquired glomerular diseases.

The mechanism by which glucocorticoids govern antiproteinuric effect in nephrotic syndrome remains unknown. Present study examined the protective role of dexamethasone (DEX) in the intracellular trafficking of nephrin under endoplasmic reticulum (ER) stress. Human embryonic kidney-293 cell line expressing a full-length human nephrin was cultured in mediums containing 5.5 or 25 mM glucose with or without DEX. The result revealed that glucose starvation evoked a rapid ER stress leading to formation of underglycosylated nephrin that was remained in the ER as a complex with calreticulin/calnexin. DEX rescued this interfered trafficking through binding to its receptor and stimulating the mitochondrial transcripts and adenosine 5' triphosphate (ATP) production, leading to synthesis of fully glycosylated nephrin. These results suggest that ER-stress in podocytes may cause alteration of nephrin N-glycosylation, which may be an underlying factor in the pathomechanism of the proteinuria in nephrotic syndrome. DEX may restore this imbalance by stimulating expression of mitochondrial genes, resulted in the production of ATP that is essential factor for proper folding machinery aided by the ER chaperones.

Congenital malignant melanoma: a case report.

Congenital malignant melanoma (MM) is an uncommon condition that is defined as MM recognized at birth. Its incidence is difficult to determine because of the small number of reported cases and because of problems associated with diagnosis. Generally, Spitz naevus and melanoma have many clinical and histopathological similarities, so it is difficult to differentiate between the two. We describe a rare case of congenital MM in which differential diagnosis from Spitz naevus was problematic. In addition, we review the literature and comment on the prognostic differences among the three types of congenital and infantile MM.

Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis.

Apoptosis induced by nonsteroidal anti-inflammatory drugs (NSAIDs) is involved not only in the production of NSAID-induced gastric lesions but also in the antitumor activity of these drugs. The endoplasmic reticulum (ER) stress response is a cellular mechanism that aids in protecting the ER against ER stressors and is involved in ER stressor-induced apoptosis. Here, we examine the relationship between this response and NSAID-induced apoptosis in cultured guinea-pig gastric mucosal cells. Exposure of cells to indomethacin, a commonly used NSAID, induced GRP78 as well as CHOP, a transcription factor involved in apoptosis. Three factors that positively regulate CHOP expression (ATF6, ATF4 and XBP-1) were activated and/or induced by indomethacin. NSAIDs other than indomethacin (diclofenac, ibuprofen and celecoxib) also induced CHOP. Monitoring of the transcriptional activities of ATF6 and CHOP by luciferase assay revealed that both were stimulated in the presence of indomethacin. Furthermore, indomethacin-induced apoptosis was suppressed in cultured guinea-pig gastric mucosal cells by expression of the dominant-negative form of CHOP, or in peritoneal macrophages from CHOP-deficient mice. These results suggest that ER stress response-related proteins, particularly CHOP, are involved in NSAID-induced apoptosis.

Survey of nasal colonization by, and assessment of a novel multiplex PCR method for detection of biofilm-forming methicillin-resistant staphylococci in healthy medical students.

We surveyed the prevalence of nasal colonization by biofilm-forming methicillin-resistant staphylococci in healthy medical students, who had never had contact with patients, using polymerase chain reaction (PCR) to detect themec A gene, production of penicillin-binding protein 2' (PBP2'), and quantitative assay of biofilm formation on polystyrene. Anterior nasal swabs from 90 students were cultured on mannitol salt and oxacillin salt screening agar plates. In total, 231 staphylococcal isolates belonging to 10 species from 88 students were identified, of which 139 from 77 (88%) students were Staphylococcus epidermidis. The overall prevalences of methicillin-resistant and biofilm-forming staphylococci were 48% (43 of 90) and 59% (53 of 90) for the medical students, respectively. In total 30 (33%) students carried biofilm-forming methicillin-resistant staphylococci in the nares, all of which were identified as S. epidermidis. For rapid detection of biofilm-forming methicillin-resistant S. epidermidis (MRSE), we devised a novel multiplex PCR method to assess a total of 243 staphylococcal isolates, including the 231 isolates from the students. The multiplex PCR assay used six primers to amplify atl E and ica ADB, which are responsible for the biofilm formation ofS. epidermidis, and mec A genes. The multiplex PCR assay revealed that 68 (96%) isolates were detectable in 71 biofilm-forming MRSE isolates, which corresponded to 93% (28 of 30) of biofilm-forming MRSE carriers. Surveillance of nasal colonization with biofilm-forming MRSE using this multiplex PCR in healthcare workers and patients, might provide useful information for the establishment of infection control procedures toward biofilm-forming MRSE.

Eosinophilic pustular folliculitis in association with nevoid basal cell carcinoma syndrome.

This study reports on the clinical and light microscopic features of a nevoid basal cell carcinoma syndrome with the complication of eosinophilic pustular folliculitis. To the authors' knowledge, this is the first report of such an association, which is possibly due to immune dysregulation. Moreover, the patient experienced remission of eosinophilic pustular folliculitis after removal of the jaw cyst. One possible explanation for the remission is that a long-lasting TH, type inflammatory response as a result of the bone defect produces effective cytokines such as interferon-gamma.

The effect of nutritional status on morbidity in COPD patients undergoing bilateral lung reduction surgery.

BACKGROUND: Although candidates for lung reduction surgery (LRS) include malnourished patients with severe chronic obstructive pulmonary disease (COPD), the impact of preoperative nutritional status on surgical outcome has not been clearly elucidated. METHODS: We investigated the relationship between preoperative nutritional status and postoperative morbidity in 23 consecutive patients undergoing LRS. The percentage of ideal body weight (%IBW) and body mass index (BMI) were calculated, and fat-free mass (FFM) and fat mass (FM) were measured using a bioelectrical impedance analyzer. FFM and FM were expressed as height-normalized indices, FFM index [FFM (kg)/height (m)(2), or FFMI] and FM index [FM (kg)/height (m)(2), or FMI]. Serum levels of total protein and albumin were also determined. RESULTS: 8 patients had major complications. Preoperative %IBW and FFMI were significantly lower among patients with major complications, while no significant differences were observed in pulmonary function, FMI or serum protein. The complication rate was significantly higher among patients with low FFMI (FFMI < or = 16) but not with low %IBW or BMI. CONCLUSION: These results suggest that FFM depletion is an excellent predictor of unacceptable postoperative complication following LRS.

Markedly increased nasal blockage by intranasal leukotriene D4 in an experimental allergic rhinitis model: contribution of dilated mucosal blood vessels.

We examined whether nasal hyperresponsiveness to leukotriene (LT) D4 is seen in our allergic rhinitis model, which showed sneezing and biphasic nasal blockage by repeated antigen inhalation challenge, and whether a dilatation of mucosal blood vessels contributes to this hyperresponsiveness. Nasal blockage [increase of specific airway resistance (sRaw)] was indexed as nasal (hyper)responsiveness. The sensitized-challenged guinea pig showed a remarkable dose-dependent increase in sRaw by intranasal instillation of LTD4 (10 microl/nostril) at 10(-10) to 10(-6) M 10 h and 2 days but not 7 days after the challenge. The increase in sRaw induced by LTD4 was largely blocked by pranlukast or naphazoline, and this was dose-dependently suppressed by N(omega)-nitro-L-arginine methyl ester. Sodium nitroprusside induced an elevation of sRaw in the sensitized-challenged animal in the hyperresponsiveness state, but the degree did not differ from that in the non-sensitized-non-challenged group. The amount of NO2- and NO3- in nasal cavity lavage fluid after LTD4 instillation in the sensitized-challenged animal in the hyperresponsiveness state was significantly greater than that before the instillation. These results demonstrate that the hyperresponsiveness to LTD4 acquired by repeated antigen challenge is mainly due to dilatation of nasal blood vessels, which can be related to hyperproduction of nitric oxide through cysteinyl LT1-receptor activation.

Fatal diffuse atheromatous embolization following endovascular grafting for an abdominal aortic aneurysm: report of a case.

A 78-year-old woman with an abdominal aortic aneurysm, 57 mm in diameter, was admitted to our hospital for endovascular grafting. Preoperative computed tomography and angiography showed friable mural thrombus in the suprarenal and infrarenal aorta, and a diagnosis of shaggy aorta was made. Postoperatively, the patient suffered cerebral infarction, and disseminated intravascular coagulopathy with multiple organ failure developed, resulting in early death on the third day after surgery. An autopsy revealed diffuse atheromatous embolization into the celiac, superior mesenteric, bilateral renal, bilateral hypogastric (trash buttock), and peripheral arteries. This case report serves to demonstrate that an abdominal aortic aneurysm with a shaggy aorta in the proximal neck is a contraindication to endovascular grafting, and that predicting the possibility of diffuse atheromatous embolization by detecting a shaggy aorta is the best way to prevent this catastrophic complication.

Plasma levels of amino acids and hypermetabolism in patients with chronic obstructive pulmonary disease.

Plasma levels of amino acids were measured by ion-exchange, high-pressure liquid chromatography in 30 ambulatory patients with chronic obstructive pulmonary disease (COPD; mean +/- SD: age 64 +/- 13 y and forced expiratory volume in 1 s [FEV1] 0.85 +/- 0.25 L) and 30 age- and sex-matched healthy control subjects with regard to nutritional status, resting energy expenditure (REE), and pulmonary function. The ratio of branched-chain amino acids to aromatic amino acids was significantly (P < 0.001) decreased in COPD patients and was significantly correlated with percentage of ideal body weight (r = 0.403, P < 0.05), percentage of arm-muscle circumference (r = 0.492, P < 0.01), and %FEV1 (r = 0.467, P < 0.05). Plasma levels of alanine and cysteine were decreased, whereas levels of glutamine, aspartic acid, serine, and ornithine were elevated in COPD patients as opposed to control subjects. The ratio of resting energy expenditure to predicted resting energy expenditure was negatively correlated with the ratio of branched-chain to aromatic amino acids (r = -0.716, P < 0.01), percentage of arm-muscle circumference (r = -0.770, P < 0.05), %FEV1 (r = -0.839, P < 0.01), and the maximal inspiratory pressure (r = -0.803, P < 0.001). Underweight COPD patients also exhibited a greater degree of hyperinflation (percentage of residual volume = 205 +/- 15 for underweight patients and 156 +/- 8 for normal-weight patients). In conclusion, a decrease in plasma levels of branched-chain amino acids in relation to hypermetabolism, possibly resulting from the severity of COPD and respiratory muscle weakness, and various disturbances in plasma amino-acid levels were found in underweight COPD patients.

Spatial and temporal expression of basic fibroblast growth factor protein during wound healing of rat skin.

BACKGROUND: Basic fibroblast growth factor (bFGF) stimulates the mitogenesis of various cells and plays a key part in wound healing. OBJECTIVES: To determine the spatial and temporal expression of bFGF protein during wound healing after burning of rat skin. METHODS: Immunohistochemical methods were used. RESULTS: The immunostaining for bFGF in the normal epidermis was faint and sporadic in the basal cell layer. However, significant staining for bFGF was found in four locations: regenerated epidermis, a band-like zone near the regenerated epidermis, renewed capillaries, and cells infiltrating into the granulation tissue at the inflammatory to proliferative stages after the burn. The intensity of immunostaining of regenerated epidermis, the band-like zone and renewed capillaries was maximal during the proliferative stage and decreased to normal levels or disappeared simultaneously with wound closure. Immunopositive macrophage-like cell numbers in the granulation tissue increased during the proliferative stage and promptly decreased after wound closure, but such cells were only poorly visible in the scar tissue until 42 days postburn. CONCLUSIONS: bFGF may affect the proliferation, differentiation and migration of regenerated keratinocytes and the recruitment of inflammatory cells, as well as neovascularization in granulation tissue during wound healing. Macrophages may play a pivotal role in cutaneous wound repair by producing bFGF not only during the inflammatory or proliferative stages but also during the remodelling stage.

Stereoscopic display of a three-dimensional image of the larynx using high-speed helical scanning.

To evaluate the usefulness of stereoscopic images of larynges using helical CT in stereo mode, a retrospective review of the characteristics of stereoscopic viewing of larynges was made. The subjects were 3 patients with laryngeal cancer, 1 patient with laryngeal leiomyosarcoma and 1 patient with an advanced tongue carcinoma whose formalin-fixed larynx was extirpated. The larynges were scanned by high-speed helical CT using 1- to 2-mm slices. The reproduction of stereographic images was performed by the manipulation and rotation of three-dimensional structures around the y-axis on the computer display. The three-dimensional images of the complex structures, such as the arytenoid cartilage, aryepiglottic fold and pyriform sinus, were better observed by binocular images (stereograms) than by monocular images. Stereoscopic views of the larynx are useful in producing three-dimensional images of the unseen inner surface of the human body.