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Oxidized LDL has been obtained by incubation with copper ions (Cu-LDL) or various kinds of cells. LDL incubated with xanthoma tissues (x-LDL) is considered a model of in vivo oxidized LDL that has extravasated into xanthoma lesions. To investigate the mechanism of x-LDL formation, we studied the effects of various enzyme inhibitors or antioxidants on the oxidation process of LDL. Thiobarbituric acid-reactive substance (TBARS) levels, electrophoretic mobility and spectrophotometric pattern of the oxidized LDL were examined. Antioxidants suppressed TBARS formation in both x-LDL and Cu-LDL. Enzyme inhibitors inhibited TBARS levels in x-LDL, but not in Cu-LDL. All the enzyme inhibitors and antioxidants, except for the cyclooxygenase inhibitor, inhibited the anodic electrophoretic mobility of x-LDL. The anodic electrophoretic mobility of Cu-LDL was suppressed only with antioxidants. Spectrophotometry indicated that an increase in the absorbance at 240 nm was observed in Cu-LDL, but not in x-LDL. x-LDL oxidation is primarily catalyzed by phospholipase A 2 , and subsequently generated polyunsaturated free fatty acids propagate the peroxidation. Fatty acid hydroperoxides conjugated with dienes are not synthesized in x-LDL. On the other hand, non-enzymatic oxidants, such as superoxide anion and hydroxyl radicals generate Cu-LDL with diene-conjugated fatty acid hydroperoxides.

Background Activated mast cells enhance the uptake of mast cell–derived proteoglycan–low-density lipoprotein complexes by macrophages. Objective We sought to investigate mast cell contribution to the pathogenesis of xanthoma. Methods Twenty cases of xanthelasma palpebrarum and 6 cases of tuberous xanthoma lesions were analyzed using immunohistochemical staining. Results Xanthelasma lesions contained up to 5-fold more tryptase-stained mast cells than tuberous xanthoma lesions. Tuberous xanthoma lesions especially showed extensive staining of tryptase around mast cells and within some macrophages and foam cells. More than 99% of mast cells in xanthelasma lesions contained both tryptase and chymase. Approximately 60% of mast cells represented only tryptase in tuberous xanthoma lesions where the ratio of macrophages to tryptase-stained mast cells was extremely high (15:1) as compared with xanthelasma lesions (2:1). Limitations A change in mast cell phenotype has not been necessarily proven. Conclusion Mast cells are activated under the microenvironment in which macrophages predominate rather than mast cells, which thus reflects the clinical phenotypes of xanthoma lesions.

7例の落葉状天疱瘡，1例の尋常性天疱瘡に対して血漿交換療法とステロイドパルス療法の併用療法を施行した。有用であった7例では臨床症状の改善，抗体価の減少，ステロイド投与量の減量が可能であった。併用療法を早期より積極的に施行することで臨床症状を速やかに改善させ，ステロイド剤投与量の減量が容易となり寛解維持にも好影響が得られた。併用療法は，血漿交換療法による直接的な病因抗体の除去に加え，ステロイドパルス療法によりさらに臨床症状を効果的に改善したと考えた。この併用療法は天疱瘡に対する優れた導入初期治療であり長期的予後にも好結果を与えると結論した。

Summary Background The source of accumulated lipids in the foam cells of xanthoma is primarily the lipoproteins existing in the lesional dermis. Objective This study was designated to clarify the contribution of low density lipoprotein (LDL) density substances existing in xanthoma tissue to foam cell formation. Methods An LDL density fraction was obtained from homogenized rabbit experimental xanthoma tissue. Biochemical and functional characteristics of xanthoma-extracted LDL density substance were examined. The in vivo foam cell-inducing ability of xanthoma-extracted LDL density substance was examined microscopically at the intradermal injection site. Results Xanthoma-extracted LDL density substance showed more negatively charged mobility on agarose gel electrophoresis than plasma native LDL. A small amount of aggregated material remained at the origin on agarose gel electrophoresis. Xanthoma-extracted LDL density substance contained much higher level of lipid peroxides than native LDL. Mouse peritoneal macrophages internalized xanthoma-extracted LDL density substance extensively and transformed into foam cells by incubation with xanthoma-extracted LDL density substance. Intradermal injection of the xanthoma-extracted LDL density substance induced foam cell infiltration in the skin of a normolipemic rabbit. Conclusion LDL density substances prepared ex vivo from experimental xanthoma tissue contained lipid–protein complexes that have physiochemical properties of oxidized LDL. The lipid–protein complexes were incorporated into foam cells. The substances were considered to contribute to foam cell recruitment during the persistence of xanthoma lesions.

Summary Background Xanthoma is a foam cell infiltrating lesion similar to atherosclerosis. Glycosaminoglycans and proteoglycans have long been considered to play a role in atherogenesis. Objective The purpose of this study is to investigate the role of hyaluronan, the main dermal glycosaminoglycan, in xanthoma formation. Methods The complex formation of low density lipoprotein (LDL) with hyaluronan was investigated by assaying the cholesterol level of precipitates that were formed by incubating LDL, hyaluronan and cetylpyridinium chloride in the presence of Ca 2+ . The uptake of LDL by mouse peritoneal macrophages was studied by assaying the cellular cholesterol esterification activity. The responsible receptor for the LDL internalization was examined by saturating hyaluronan receptor and blocking class A macrophage scavenger receptor (CD204). Hyaluronan was injected into the dorsal skin of diet-induced hypercholesterolemic rabbits to reveal the xanthoma inducing activity of hyaluronan. Results Cetylpyridinium chloride precipitated hyaluronan, which had formed complexes with LDL. The macrophages incorporated hyaluronan–LDL complexes and oxidized LDL via CD204. Foam cell infiltration and cholesterol accumulation were induced by intradermal injections of hyaluronan in diet-induced hypercholesterolemic rabbits. Conclusion Hyaluronan, like other sulfated glycosaminoglycans, retains LDL by forming a complex. Via macrophage scavenger receptors, macrophages incorporate not only LDL–hyaluronan complexes, but also oxidized LDL, which has been oxidized during the retention time.

We report the case of an 85-year-old man who presented with an enlarging tumor on the right temple. Histologically, spindle-shaped cells were proliferating continuously within well-differentiated squamous cell carcinoma that was immunohistochemically negative for vimentin and alpha-smooth muscle actin (ASMA) but positive for cytokeratin (AE1/3). These spindle-shaped cells expressed vimentin and ASMA but not cytokeratin (AE1/3). Intermediate cells with round nuclei and small amounts of cytoplasm displayed slight expression of vimentin, ASMA, and cytokeratin. This case illustrated spindle cell squamous cell carcinoma with mesenchymal metaplasia of malignant epithelial cells.

著明な色素沈着を伴う疣状扁平苔癬を生じた58歳の男性例を報告する。初診の2年前より血液透析を受けており，7ヵ月前より数種類の薬剤を内服していた。5ヵ月前より背部を主体に全身性，左右対称性に紫紅色丘疹が多発し，次第に黒色丘疹と疣状の灰白色小結節および局面が擦過部位に目立つようになった。病理組織像は扁平苔癬に合致し，黒色丘疹部では表皮内メラニンの増加とメラノファージ浸潤が著しく，灰白色局面では表皮肥厚が顕著で，表皮内メラニンは乏しく，メラノファージも少なかった。薬剤誘発性と考え，血液透析は継続しつつ，内服薬を中止または他剤に変更し，プロピオン酸クロベタゾール軟膏の外用を行うことにより皮疹は消退し，再発しなかった。パッチテストおよび内服誘発試験では原因薬剤は特定できなかった。著明な色素沈着は，血液透析で除去されず体内に高濃度に蓄積されたβ-lipotropinがメラニン産生を著しく増強させた結果と考えた。

A 15-year-old boy first noticed multiple firm papules on his right upper chest two years before presenting to our clinic. These papules were densely distributed and showed epidermal nevus-like linear arrangement at some sites. The number, size, and distribution of these papules remained unchanged for one year of our observation. The papules flattened leaving scars and did not recur within a year after one shaving abrasion using a scalpel. Histopathologically, epidermis of the papule displayed acanthosis with elongated rete ridges. Accumulation of mucin was apparent in the papillary and subpapillary dermis. In mucinous nevus, the origin of cells with nevoid proliferation is obscure. In contrast with common collagenous connective tissue nevus, it is hard to define the localized persistent mucin accumulation as a nevoid manifestation. The present case of mucinous nevus might be caused by significantly stimulated glycosaminoglycan synthesis in a kind of epidermal nevus without extreme hyperkeratosis.

53歳，女性。下顎では色素沈着を残し，下腿では色素沈着を残さない固定薬疹が繰り返し出現した。パッチテスト(皮疹部および無疹部)およびスクラッチパッチテスト(無疹部)は陰性。ミノサイクリン5mg投与による内服誘発テストでは，下顎と下腿に皮疹が再燃し，前額にも紅斑が新生した。病理組織像では下腿に比べ下顎の真皮にメラノファージが著明に多く認められた。免疫組織化学では，トリプターゼ陽性肥満細胞が下腿と比較して下顎の特に真皮乳頭層において有意に多く認められた。肥満細胞由来のケミカルメディエーターやサイトカインが，メラノサイトのメラニン合成やメラニンのケラチノサイトへの輸送を促進することも色素沈着を増強させる因子であると考えた。

53歳, 女性。D-ペニシラミンの内服開始1年4カ月後, 肉眼的には落葉状天疱瘡, 病理組織学的には尋常性天疱瘡の所見を示す皮疹を生じた。免疫ブロット法で, デスモグレイン (Dsg)-1抗体が証明されたが, Dsg-3抗体は認められなかった。ELISA法では, Dsg-1およびDsg-3抗体ともに陽性だった。内服中止後も水疱の新生は続いた。プレドニゾロンの内服減量中に水疱が再燃した際には, Dsg-3抗体は陰性化していたがDsg-1抗体は陽性であったことから, Dsg-3抗体は薬剤によって修飾されたDsg-3に対する抗体であり, Dsg-1抗体は持続的に産生されていると考えた。抗核抗体と抗細胞質抗体が陽性であったことから, 自己抗体を産生しやすい素因があると考えた。水疱蓋および水疱内の多くの棘融解細胞が変性していたことも特徴であった。

Human low density lipoprotein (LDL) was incubated with rabbit xanthoma tissue or non-lesional dermis. The xanthoma tissue-modified LDL (x-LDL) was oxidized showing a 12-fold higher level of thiobarbituric acid-reactive substances (TBARSs) and a faster anodic electrophoretic mobility than native LDL (n-LDL). The LDL treated with non-lesional dermis (d-LDL) had a twofold higher TBARS level compared with n-LDL, but the electrophoretic mobility of d-LDL and n-LDL was similar. Cholesterol esterifying activity in mouse peritoneal macrophages, an indicator of LDL uptake, was up-regulated 5-fold and 1.8-fold by incubation with x-LDL and d-LDL, respectively, compared with n-LDL. Macrophages transformed into foam cells in incubation with x-LDL, and intradermal injections of x-LDL induced infiltration of great many foam cells in the normolipemic rabbit dermis. d-LDL had much less effects on the foam cell formation and foam cell infiltration than x-LDL. Cholesterol:protein ratio was higher in x-LDL than in n-LDL and d-LDL, suggesting that x-LDL-induced foam cells accumulated the lipids by incorporating the cholesterol-rich x-LDL. In conclusion, extravasated LDL receives oxidation and contributes to foam cell recruitment in xanthoma lesions. On the other hand, extravasated LDL in non-lesional dermis receives limited oxidation and additional promoting factors are necessary for initiation of xanthoma development.

Repeated ultraviolet (UV) irradiations have been shown to induce keratinocyte proliferation with acanthosis, stimulate the cutaneous nerve proliferation, and increase the synthesis of calcitonin gene-related peptide (CGRP). In the current study, we examined the role of CGRP in the UVB-induced proliferation of murine keratinocytes. UVB irradiation increased the number of bromodeoxyuridine (BrdU)-labeled basal keratinocytes and caused acanthosis. In addition, CGRP expression was up-regulated in the peripheral nerves of the upper dermis and lower epidermis. Repeated intradermal injections of CGRP increased the number of BrdU-labeled basal cells and caused acanthosis. Intradermal injections of capsaicin prior to UVB-irradiation inhibited the UVB-induced CGRP expression, BrdU labeling in basal keratinocytes and epidermal thickening. Intradermal injections of anti-CGRP antibody inhibited the UVB-induced BrdU labeling in basal keratinocytes, but epidermal thickening was not significantly inhibited. These results indicate that CGRP is one of the stimulators to UVB-induced keratinocyte proliferation. On the other hand, expression of substance P, another neuropeptide in the peripheral nerve, was not up-regulated by UVB irradiation.

Sujiaonori, a river alga growing in the Kochi prefecture, Japan, contains several bioactive compounds such as sulfated polysaccharides (ulvans), ω-3 fatty acids, and vitamins. Dietary intake of this alga-based supplement has been reported to increase circulatory adiponectin, a salutary hormone that is reported to be associated with healthy longevity and prevents a number of cardiovascular and metabolic disorders. This report highlights the anti-allergic and skin health enhancing effects of Sujiaonori-derived ulvan (Tosalvan) and supplement, respectively. RBL-2H3 cell line was used to investigate the anti-allergic effect of algal SP through the evaluation of β-hexosaminidase activity. Algal sulfated polysaccharides or SP (Tosalvan, Yoshino SP) were extracted from powders of dried alga samples provided by local food manufacturers. Report on the effect of daily dietary intake of Sujiaonori-based supplement on skin health is part of a four-week clinical investigation that, in comparison with a supplement made of 70% corn starch powder and 30% spinach powder mixture (twice 3 g daily), explore the beneficial effects of Sujiaonori algal biomaterial (SBM; 3 g taken twice daily) on cardiovascular, gastrointestinal and skin health in a sample of Japanese women. Transepidermal water loss (TEWL) was the skin health marker used in this study and was measured with the use of a corneometer. Significant reduction of β-hexosaminidase activity was observed in Tosalvan and Yoshino SP-treated cells (vs. control; p < 0.05), whereas dietary intake of SBM markedly reduced TEWL level after four weeks of supplementation, as compared to baseline TEWL (p < 0.001). Additionally, SBM improved TEWL better than the control product (p < 0.001). Findings contained in this report suggest that Sujiaonori-derived Tosalvan and Yoshino SP have anti-allergic potential and that the dietary intake of SBM has a beneficial effect on skin health.

Constipation is a gastrointestinal motility disorder that represents a major health problem in Japan. Approximately 26% of young Japanese adult women are reported to have this complaint. We report on the health effects of daily intake of Sujiaonori algal biomaterial (SBM) on constipation on 12 Japanese adult women. Data are from a four-week dietary intervention study on the health effects of daily Sujiaonori supplementation on cardiovascular, skin, and gastrointestinal health in which 32 adult Japanese volunteers (age range: 20–54 years) participated. They underwent clinical and laboratory investigations, and completed two study questionnaires (the brief diet history questionnaire (BDHQ) and the current health questionnaire) before and after dietary intervention. Of the 12 women volunteers with functional constipation, there were six SBM-supplemented subjects who received 3 g of Sujiaonori powder twice daily during meal, whereas the six others (controls) were from the group of those who took 3 g of a power made of 70% corn starch and 30% Japanese spinach mixture. The analysis of data on daily nutrient intake showed no significant dietary changes for nutrients (minerals, proteins, fiber, fat) and calorie intake (except alcohol intake that was reduced) in both groups. In SBM group, a significant reduction of the proportion of women with constipation was observed (p < 0.001), whereas no significant change was noted within the control group (p > 0.05). When both groups were compared, SBM was more effective than the control product; 66.7% (4/6) of SBM-supplemented women had their constipation relieved, whereas only one control (16.7%) controls benefited from dietary intervention (p < 0.001). In addition, no adverse effect was reported in the SBM group, whereas two controls reported nausea at post-survey. These results suggest that Sujiaonori contains compounds that can improve gastrointestinal function and relieve constipation.

Infrasternal mediastinoscopic single-incision surgery is a minimally invasive surgical option for patients with anterior mediastinal lesions. The main drawback of the procedure is difficult when handling the endoscopic instruments through the small infrasternal incision. Herein, we report our initial experience with use of the procedure in 2 patients with bronchogenic cysts in the anterior mediastinum. We found that use of an SILS Port, now widely available for single-incision laparoscopic surgery, can decrease the difficulty of this approach.

We report the outcomes of palliative surgery for the treatment of malignant bowel obstruction in patients with advanced gastroenterological cancer. We studied 20 patients who had undergone palliative surgery over 3 years. We analyzed the clinical findings, surgical procedure, postoperative clinical course, and prognosis. The origin of the patients was colorectal cancer( 9 cases), gastric cancer( 4 cases), uterine cancer( 3 cases), pancreatic cancer( 2 cases), bladder( 1 case), and anal cancer (1 case). Small bowel obstruction was noted in 8 cases and colorectal obstruction was noted in 14 cases. Colostomy was performed in 13 cases, resection and reconstruction were performed in 6 cases, and bypass was performed in 4 cases. Ninety percent of the patients were able to eat solid food following the surgery, but 20% of the patients were forced to have bowel obstruction. The median survival time after palliative surgery was 3 (range, 0-15) months, and 6 patients (30%) died within 2 months. We concluded that palliative surgery for the treatment of malignant bowel obstruction could improve the patients' quality of life. The decision for performing palliative surgery should be made while considering the patient's prognosis, wishes, and potential for symptom improvement.

Peripancreatic head cancer often causes obstructive jaundice and duodenal obstruction, which reduces the quality of life and hinders the administration of anti-cancer drugs. Here, we report 4 cases of double bypass surgery( biliary and gastric) for the treatment of inoperable peripancreatic head cancer. The patients' ages ranged from 64 to 72 years. Two patients had pancreatic head cancer and 2 had ampullary cancer. No postoperative morbidity was observed and all 4 patients resumed oral intake within 5 days after surgery and began receiving chemotherapy within 1 month after surgery. There was immediate relief of biliary obstruction in all 3 patients with obstructive jaundice. None of the patients experienced recurrence of obstructive jaundice requiring biliary drainage. Two patients who died of cancer were able to consume food orally just before they died. Although bypass surgery is more invasive than endoscopic stenting, it may be safe and useful not only for palliation, but also for induction or continuation of chemotherapy.

Steroid hormone receptors are composed of six major functional domains, i.e. the A/B domains as the activation function 1 domain (AF-1), domain C as the DNA-binding domain, domain D as a hinge domain and domain E/F as the ligand-dependent transcriptional domain (AF-2). They regulate gene transcription through interactions with various nuclear factors of their domains, such as AF-1 and AF-2. We have insufficient knowledge of the function of the DNA-binding domain (domain C) except for its DNA-binding function or the hinge domain (domain D). Therefore, we attempted to identify factors interacting with the domains by using a yeast two-hybrid system. Domains C and D of estrogen receptor α were used as a bait to isolate cDNA clones from a rat ovary cDNA library. We isolated the cDNA clone of a novel steroid receptor-binding protein bearing the regulator of G-protein signaling (RGS) designated as SRB-RGS. The protein repressed the transcriptional activity of estrogen receptor α, suggesting cross-talk of steroid hormones and peptide hormones (or growth factors) for signal transductions mediated by SRB-RGS.

A 53-year-old female developed erythema elevatum diutinum (EED) twelve years after the onset of rheumatoid arthritis. The arthritis had been well controlled for the last several years. Annular purpuric macules were characteristically complicated by common nodular and plaque lesions. Both leukocytoclastic vasculitis and fibrosis were observed in the macular lesions, indicating that the lesions were a manifestation of an early phase of EED. Both types of skin lesions disappeared with treatment with dapsone. They have not relapsed for two years after stopping the dapsone. The leukocytoclastic vasculitis was thought to have developed independently of the rheumatoid arthritis. She had noticed sicca symptoms two years before the appearance of EED, but she did not satisfy the diagnostic criteria for Sjögren's syndrome.

38歳, 男性。深部静脈血栓症による下腿潰瘍を呈した。抗カルジオリピンβ2グリコプロテインI抗体, ループスアンチコアグラントおよび抗核抗体陽性で, 原発性抗リン脂質抗体症候群と考えた。通常の治療では難治であった潰瘍は, ワーファリン®とブコローム内服により短期間で治癒した。ワーファリン®単独投与では効果が不十分な場合には, トロンボテストを指標にブコロームを併用することが重要である。潰瘍再発の4ヵ月前に小腸イレウスを発症し, Degos病類似の皮疹が出現したが, 腸穿孔はなく, 皮疹の病理組織像には特徴的な所見は認められなかったことから, 抗リン脂質抗体症候群に伴うDegos病様症候と考えた。

A 52-year-old man with squamous cell carcinoma (SCC) complicated with pseudoepitheliomatous hyperplasia on the tongue is reported. Six times biopsies obtained from the tumors of the dorsal aspect of the tongue revealed no malignant changes in the hypertrophic epidermis. Histological findings of lichen planus were observed on a part of the tumors. Dental crowns containing patch test-positive mercury were irritating the ulcerating portion of the tumors. Serum SCC antigen level was elevated. The tumors regressed by administration of etretinete, but serum SCC antigen level was unchanged. After stopping the administration, the tumors proliferated again. Histological findings of SCC were observed in a biopsy sample obtained from the floor of the tongue. Serum SCC antigen was decreased after the tumors were resected. Lichen planus or irritations by dental crowns might have caused the SCC. Tongue carcinoma preferentially appears on the side and floor of the tongue. We have to be nervous to the biopsy site of tongue tumors.

A 71-year-old Japanese man presented with asymptomatic, firm, brown-red papules on the dorsum of his left hand and back. A biopsy specimen revealed granulomatous infiltration consisting of multinucleated giant cells and histiocytes in the upper dermis. Elastic fibers were absent in the upper dermis, having been phagocytosed by giant cells. These papular elastolytic giant cell granuloma lesions regressed very well with narrow-band ul traviolet B irradiation, with only residual brown pigmentation left after treatment.

For the purpose of treating intractable decubitus and skin ulcer, streptokinase (SK) jellies containing different types of thickening agents were prepared. Adhesion to the affected sites, the spreading ability of the jelly preparation, and the properties of the SK in the jelly, which are all considered to greatly affect the clinical efficacy, were examined pharmaceutically using the viscosity, spreading area, and release and stability of SK as indexes. Regarding the viscosity and spreading area which are thought to affect both adhesion and spreading greatly, when sodium polyacrylate (PANa) was used as a thickener, higher viscosity and smaller spreading area were obtained in comparison with carboxymethylcellulose sodium (CMCNa) and sodium alginate (Alg Na). In addition, the viscosity and the spreading area obtained with PANa were also slightly more affected by temperature than with CMCNa and AlgNa. Regarding the release of SK from the jelly preparations, with PANa no initial burst was observed and SK was continuously released at a constant rate in contrast with CMCNa and AlgNa, thus obviously showing the superiority of PANa in the retention of SK. Although no loss of the potency of SK was found in the jellies containing PANa, CMCNa or AlgNa at 5°C, for 30 days, the remaining potency was greatly decreased to 49-62% at 25°C after 30 days and 33-42% at 37°C after 30 days. These results showed that the adhesion, spreading ability and SK-release were greatly different among the tested thickening agents, and the properties of PANa were found to be clearly superior to those of the other agents. According to these results, SK jelly containing 2% PANa was used for the treatment of intractable decubitus and skin ulcer, and an excellent therapeutic effect was obtained.

A rare case of papular mucinosis on the back of a 78-year old man is described. The patient developed approximately 20 discrete papules on the upper back. His serum glucose concentration was borderline elevated, but no other systemic symptoms or signs were apparent. A biopsy revealed mucin deposits only in the upper reticular dermis. The papules were distinctly different from lichen myxedematosus in clinical and histochemical appearance. The present case may represent very early-stage lichen myxedematosus complicated by borderline diabetes mellitus.

Liquid chromatography-atmospheric-pressure chemical ionization mass spectrometry (LC-APCI-MS) of some plant triglycerols gave mass spectra with the peaks of [M + H] + and [M - R 1 (R 3 ) COOH + H] + ions, in which [M + H] + and R 1 (R 3 )COOH represent, respectively, the protonated molecular ion and fatty acid at the sn-1-(or -3-)position of the triacylglycerol. It was possible to discriminate fatty acids between sn-1-(or -3-) and -2-positions. The ratio of the molecular extinction coefficient (e) of triacylglycerol at 220 nm to that of cholesterol depended on the total number of double bonds in the triacylglycerol. Thus, triacylglycerols in naturally occurring oils could be determined by using LC-APCI-MS with spectrophotometry. LC-APCI-MS of hydroperoxidized triacylglycerols gave characteristic fragment ions [M - H 2 O 2 + H] + , [M - H 2 O + H] + and [M - R 1 (R 3 ) COOH - H 2 O 2 + H] + .

Two patients with disseminated superficial porokeratosis (DSP) with amyloid deposition are reported. The skin lesions were distributed over both sun-exposed areas and sun-protected areas. No exacerbation by sun exposure was noted. Abundant amyloid substances were deposited at the papillary dermis, not only beneath the cornoid lamellae but also within the annular margin. The skin lesions and amyloid deposition regressed with topical application of dimethyl sulfoxide in one patient, suggesting that DSP is one of the clinical phenotypes of primary localized cutaneous amyloidosis. Another possibility is that amyloid substances are produced by poorly differentiated keratinocytes in DSP.

33歳, 男性。初診8カ月前に右側頭部に紅色腫瘤が出現した。病理組織学的に悪性度の高い悪性線維性組織球腫と考えた。転移所見は確認できなかった。しかし, 将来再発や転移の可能性が高いと予測されたので, 全摘後, シスプラチンとアドリアマイシンにカフェインを併用した化学療法を3クール行った。術後1年3カ月現在, 局所再発や遠隔転移はみられていない。

40歳の男性。全身諸処に有痛性の丘疹および周辺堤防状に隆起する暗紅色結節が散在, 一部では虫喰い状の潰瘍となり排膿を認めた。生検組織像では, 表皮はpseudoepitheliomatous hyperplasiaを示し, 真皮では膿瘍形成を伴う多数の好中球浸潤を主体とする肉芽腫形成を認めた。細菌培養では無菌性のことが多かったが, 時に二次感染としてS. epidermidis, S. aureus, E. faecalisが検出された。抗酸菌培養および真菌培養は陰性, 白血球減少, 単球増加, 好中球機能低下を認め, 骨髄像より慢性骨髄単球性白血病(CMMoL)と判明。CMMoLによる好中球機能低下を基盤とした壊疽性膿皮症と診断した。ミノサイクリンは皮疹に対してある程度有効であったが, 他の抗菌剤は無効。プレドニゾロンは用量依存性に奏効し, 皮疹は瘢痕治癒するものもあり, 自潰して潰瘍となることは抑制できた。しかし糖尿病の合併により, 充分量投与できなかったため, 新しい結節の出現を完全には抑制できなかった。G-CSFを投与するも, 汎血球減少症および皮疹は改善されず, 肺炎を併発して死亡した。

The value of chemoradiation therapy (CRT) followed by surgery is unknown in Japan.Thirty Patients with TNM cStage II - III squamous cell carcinoma (SCC) of the esophagus were divided into CRT (40 Gy) followed by surgery( arm A) and definitive CRT( 60 Gy()arm B). The correlations between several clinicopathological factors and survival time were examined.The effective rate (CR+PR) of CRT was 75% in arm A versus 88.9% in arm B (p= 0.32). There was no significant difference about the median survival time (arm A: 17. 4 months, arm B: 12. 6 months, p= 0.18). The two-year survival rate was 40 . 4% in arm A versus 41 . 6% in arm B (p=0.35).Our retrospective study showed no significant difference in prognosis between CRT followed by surgery and definitive CRT. Definitive CRT might be a choice of therapy for curative esophageal carcinoma.

We reviewed the patients with neoadjuvant chemoradiotherapy (CRT) with S-1 to evaluate the feasibility and effectiveness for locally advanced lower rectal cancer. The CRT regimen consisted of pelvic irradiation (45 Gy in fractions of 1.8 Gy), five days a week. A treatment of oral S-1 (80 mg/m2 per day) on days 1-14 and 22-35 was given during radiotherapy. Patients underwent a curative resection with lateral lymph node resection at 6-8 weeks intervals after neoadjuvant CRT. The response rate on pathological study was 60% (all were grade 2), and no patients had lateral lymph node metastases. Grade 1 or 2 adverse effects occurred in all patients during CRT, but the CRT was achieved in all patients. We found two patients had surgical complications with wound infection and one patient with anastomotic leakage. All complications were improved by conservative treatment. The neoadjuvant CRT was feasible and effective treatment for all patients with locally advanced rectal cancer. We have started a phase II study of the neoadjuvant CRT.

The patient was an 80-year-old woman who was diagnosed with locally advanced low rectal cancer. It was unresectable and we performed chemoradiotherapy combined with S-1 (S-1 80 mg/m2, RT 1.8 Gy × 25, total 45 Gy). An effective reduction of primary region resulted in curative resection (super low anterior resection, D3 lymph node dissection, covering ileostomy) with preserving the anal sphincter. Histopathologically, therapeutic efficacy was Grade 2. Preoperative chemoradiation has been a standard therapy in Western countries and would control local recurrence. This case indicated that CRT could improve a rate of curative resection in patients with locally advanced rectal carcinomas.

Many kinds of authentic fatty acids, including hydroperoxy and hydroxy acids, were found to be not only detectable by liquid chromatography-mass spectrometry (LC-MS) with an atmospheric pressure chemical ionization interface system, but also measurable quantitatively by LC-MS installed with a spectrophotometer. We used LC-MS with spectrophotometry to analyse fatty acids split from lecithins after phospholipase A 2 treatment. Thus, some hydroperoxy fatty acids split from photo-oxidized lecithin could be identified.

Epidermal keratinocytes in psoriatic lesions are characterized by activated Stat3, and increased levels of cytokines and growth factors that promote Stat3 activation have been found within psoriatic lesions. K5.Stat3C transgenic mice, in which keratinocytes express a constitutively active Stat3, develop psoriasis-like skin lesions. In this study, we examined whether STA-21, a small Stat3 inhibitor, could be useful in ameliorating the skin lesions not only in the model mouse but also in human psoriasis. Treatment with STA-21 markedly inhibited the cytokine-dependent nuclear translocation of Stat3 in normal human keratinocytes in vitro. Keratinocyte proliferation was inhibited by STA-21 in a dose-dependent manner through downregulation of c-Myc and cyclin D1, whereas involucrin, transglutaminase 1, and keratin 10 levels were upregulated. Topical application of STA-21 abolished the generation of skin lesions in K5.Stat3C mice. Finally, we treated psoriasis patients with STA-21-containing ointment in a nonrandomized study. Psoriatic lesions in six of the eight patients showed improvement after topical STA-21 treatment for 2 weeks. Therefore, we conclude that targeting Stat3 may lead to a therapy for psoriasis.

A case of non-clostridial gas gangrene (NCGG) developing in a plantar recalcitrant ulcer associated with diabetes mellitus (DM) is reported. A 63-year-old female was admitted to the hospital, because of a recalcitrant ulcer in the right first toe associated with DM. Following admission her right foot swelled, and plantar gangrene, excretion of pus with a foul smell, crepitation on pressing, and a gas picture on XP were noted. Therefore, a diagnosis of NCGG was made. Conservative treatment including administration of antibiotics and random skin cutting was carried out. However, her right leg was amputated after CT indicated expansion of the gas picture. NCGG often occurs in association with such underlying diseases as DM. Since this patient did not have her DM under adequate control, it is thought that the ulcer in the right first tow was the source of infection for the NCGG. The pathological progression of NCGG is relatively gradual, and the suitable period when it can be cured may be easily missed. Prognosis may become unfavorable. It is important to determine the causative bacteria in an early stage by gram-staining of the pus in order to make the differential diagnosis between NCGG and clostridial gas gangrene (CGG). If a curative tendency by conservative treatment is not observed, one should not hesitate to amputate the affected limb.

We developed a new radiosensitization treatment using a hydrogen peroxide solution (Oxydol)-soaked gauze named KORTUC I (Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas) for superficially exposed and unresectable neoplasms, such as malignant melanoma and malignant fibrous histiocytoma (MFH), based on our experimental results which demonstrated hydrogen peroxide as a strong radiosensitizer for the highly radioresistant osteosarcoma cell line, HS-Os-1. Five patients entered our clinical trial, one of whom had unresectable malignant melanoma; one, unresectable MFH; one, unresectable extramammary Paget's disease; one, locally advanced breast cancer and one with locally recurrent skin cancer. These patients were treated with radiation therapy using a high-energy electron beam from a linear accelerator. The total dose was 48 Gy, and each fraction size was 4 Gy. Radiation therapy for these patients was performed three times per week. Each time the radiation therapy was carried out, the superficially exposed tumors of these patients were covered with hydrogen peroxide solution (Oxydol)-soaked gauze, and the lesion was gently massaged for several minutes so as to allow the hydrogen peroxide solution to soak deeply into the tumor. In the treatment results, two of these five patients showed a clinically complete response (cCR) two to three months following the end of the KORTUC I radiosensitization treatment. The other three patients showed a clinically partial response (cCR) showing a decrement of more than half of the pretreatment volume. KORTUC I was completed without any severe complications, excluding mild radiation-induced dermatitis/mucositis (Grade I). In conclusion, this newly developed radiosensitization treatment using hydrogen peroxide solution (Oxydol)-soaked gauze for superficially exposed unresectable/radioresistant neoplasms appears to be an effective and valuable method of radiosensitization in terms of the blockade of anti-oxidative enzymes such as peroxidases, resulting in local oxygen production. Moreover, the KORTUC I radiosensitization treatment is relatively inexpensive and the method can therefore be utilized worldwide for many patients suffering from superficially exposed and locally advanced radioresistant neoplasms such as malignant melanoma, malignant fibrous histiocytoma (MFH) and various types of sarcomas.

Herpetiform vesicles and erythema with erosion developed on the trunk of a 48-year-old Japanese man. Acantholysis was observed in the spinous layer of the lesional epidermis and direct immunofluorescence revealed cell surface deposition of immunoglobulin IgG and C3. Indirect immunofluorescence could not detect circulating anti-cell surface antibodies. Immunoblot analysis detected neither anti-desmoglein (Dsg)1 antibody nor anti-Dsg3 antibody. Enzyme-linked immunosorbent assay could detect IgG and IgA anti-Dsg 1 antibodies and IgA anti-Dsg3 antibody, in addition to a gray zone titer of IgG anti-Dsg3 antibody. Intraepidermal neutrophilic infiltration with neutrophilic microabscesses and intense dyskeratotic cells were histopathologically characteristic in this case. Skin lesions improved within 1 month and remission has continued for 9 years under oral administration of dapsone.

A 5-month-old boy was noted to have brown macules with palpable infiltration on the head, trunk, and extremities a few weeks after birth, with recurrent episodes of generalized flushing and blistering in some of the macules. These lesions developed into yellowish plaques after 1 year of topical treatment with clobetasol propionate. Serum lipid levels were within normal limits. The appearance of the yellowish lesions was similar to that of the xanthelasmoid type of cutaneous mastocytosis. The brown macules showed infiltration of a large number of mast cells and a small number of scattered foam cells, whereas in the yellowish plaques, the number of foam cells was greatly increased. The yellowish plaques regressed spontaneously within a year after cessation of topical corticosteroid treatment. Immunohistochemical analysis found that the foam cells were stained with monocyte/macrophage markers including HAM56, and with SRA-C6, a monoclonal antibody to macrophage scavenger receptor class A (CD204). Therefore, the yellowish plaques were considered to be plane xanthoma associated with cutaneous mastocytoma.

Background: The migration of circulating monocytes into the dermis is considered to be essential for both the initiation and the progression of xanthoma. The contribution of vascular endothelial cells to the migration process is unclear. Methods: Twenty cases of xanthelasma and six cases of tuberous xanthoma lesions were analyzed using immunohistochemical staining. Results: Xanthoma lesions contained up to 25-fold more von Willebrand factor-stained endothelial cells than normal skin. The prevalence of E-selectin-positive endothelial cells increased by up to threefold more in xanthoma lesions than in normal skin. In contrast, the prevalence of intercellular cell adhesion molecule-1 (ICAM-1) decreased up to 3.5-fold more in xanthoma lesions than in normal skin. In xanthoma lesions, almost all ICAM-1-positive endothelial cells co-expressed with E-selectin but many endothelial cells, which only expressed E-selectin, were also found in the lesions and the ratio of macrophages to endothelial cells was higher (10:1) than that in normal skin (5:1). Conclusions: Endothelial cells proliferate and express E-selectin rather than ICAM-1 under a microenvironment in which macrophages predominate rather than endothelial cells, thereby promoting macrophage migration into xanthoma lesions.

Pseudoxanthoma elasticum is an inherited systemic disorder of connective tissue characterized by fragmentation of elastic fibers and calcification in cutaneous, ocular, and cardiovascular systems. Mutation in the ATP-binding cassette subfamily C member 6 gene has recently been found in people with pseudoxanthoma elasticum (1). However, the precise mechanisms of elastic fiber fragmentation and calcification remain obscure. Recently, it has been reported that mild chronic oxidative stress affects pseudoxanthoma elasticum fibroblasts (2). This suggests that reactive oxygen scavengers might improve this disorder.

生後5日目に右足に水疱が初発し, 中心治癒傾向を示す配列をし, 瘢痕を残さず治癒する水疱が出没しているDowling-Meara型単純型先天性表皮水疱症の男児例を報告した。光顕的には表皮下水疱であったが, 電顕的には表皮内水疱および表皮基底細胞にトノフィラメントが異常凝集していることから, Dowling-Meara型単純型先天性表皮水疱症と診断した。ビタミンEの内服は無効で, 2歳の現在, 新しい皮疹の出現が続いているが, 自覚症状は乏しいらしく機嫌は良い。父親にも同症が認められたが, 小学校低学年時には寛解しており, 患児も自然軽快することが期待される。