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腹部にそう痒を伴う線状紅斑を呈した43歳の秋田県下在住の男性を生検したところ虫体が検出された。虫体の形態学的特徴より日本顎口虫の幼虫と同定された。初診時に9%の末梢血好酸球増多を示していたが, 血清IgE値は正常で, ドロレス顎口虫抗原を含む数種の蠕虫抗原に対する免疫血清診断は全て陰性であった。患者には発症前のシラウオ生食歴があるが, 感染源は不明である。病原虫体まで同定された顎口虫症は稀と思われるので報告した。

Tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2 are the enzymes involved in melanin biosynthesis and are preferentially expressed in pigment cells. Their human gene promoters share the 11-base pair M box containing a CATGTG motif, which was shown here to be bound in vitro by microphthalmia-associated transcription factor (MITF). Transient cotransfection analysis showed that MITF overexpression increased the expression of a reporter gene under the control of the human tyrosinase or TRP-1 gene promoter but not the TRP-2 promoter. The promoter activation caused by MITF is dependent on each CATGTG motif of the distal enhancer element, the M box, and the initiator E box of the tyrosinase gene and the TRP-1 M box. Furthermore, a truncated MITF lacking the carboxyl-terminal 125 amino acid residues transactivated the tyrosinase promoter less efficiently than did MITF, suggesting that MITF's carboxyl terminus contains a transcriptional activation domain, but unexpectedly such a truncated MITF remarkably transactivated the TRP-2 gene promoter. These results suggest that MITF is sufficient to direct pigment cell-specific transcription of the tyrosinase and TRP-1 genes but not the TRP-2 gene.

This article is a case report of a 78-year old Japanese woman with a history of malignant melanoma resected from her right 2nd toe followed by an ilioinguinal lymph node dissection in 1980. The lymph node dissection, however, was not quite successful, because numerous nodes were proved metastatic tumors. The histological specimen obtained from the primary lesion was found to be acral lentiginous melanoma, Clark's level III, 0.8mm in thickness, pT2N2M1a, stage IV. She underwent combination chemotherapy using DTIC, nitrosourea and vincristine (DAV) for 5 years and vaccination with BCG (Japanese lnstitute for BCG, Tokyo) for 7 years.Although metastatic tumors in paraaortic lymphnodes were not completely dissected, no evidence of distant metastases including recurrence of regional lymph node metastasis was noted prior to the appearance of intransit metastases in her right leg 13 years after the initial surgical procedures. In addition to the excision of intransit metastases, she was treated with DAV and intracutaneous injection of interferon-β. Late recurrence (i.e. 10 or more years after definitive surgery) is not unusual in malignant melanoma, but is rare in an advanced stage of melanoma such as our case.

Circulating prolactin levels in a woman with systemic lupus erythematosus (SLE) were measured over a period of 4 years, and her hyperprolactinemia remained associated with disease activity throughout. Circulating prolactin could thus be a better practical marker than standard parameters such as anti-double-stranded DNA antibodies and serum complement in some patients with SLE.

Importance Oral propranolol hydrochloride treatment has been proven effective for infantile hemangiomas. To our knowledge, this study is the first to report multiple cases in which oral propranolol therapy was used for patients with circumscribed choroidal hemangioma. Observations Five patients with circumscribed choroidal hemangioma were treated at Nagoya Medical Center, Nagoya, Japan, from 2011 to 2012. Oral propranolol hydrochloride was initiated at 10 mg 3 times a day and was increased monthly by 30 mg/d until the desired effects were observed. The mean (SD) height of the tumor (based on the B-mode at the end of the study) was 84.5% (13.6%) relative to the initial height. Similarly, the mean (SD) tumor area (based on indocyanine green angiography) was 94.2% (6.0%), the mean (SD) visual acuity was 0.04 (0.21) logMAR, and the mean (SD) Humphrey visual field mean deviation was −0.98 (1.1) dB. In 3 patients with macular edema, the mean (SD) foveal thickness (measured with optical coherence tomography) was 114.0% (13.9%). Conclusions and Relevance Although oral propranolol therapy may partially improve the condition of patients with circumscribed choroidal hemangioma, it does not seem to have a critical therapeutic effect, at least at blood concentrations lower than 50 to 100 ng/mL. Trial Registration umin.ac.jp/ctr Identifier: UMIN000006623

We propose an energy efficient demand control method for air-conditioning systems for buildings installed with multi-split packaged air-conditioning systems (PAC). Energy efficiency is improved by controlling the operating point constantly to target power consumption while limiting PAC electricity power demand and recovering a normal condition without relying on PAC internal logic. The constant operating point is determined as the ratio of the number of units requiring 100% heat load among all indoor units when all units are set to either 100% or 0% using only ordinal external interface information such as temperature setting and operating mode. The proposed method is a practical measure that enables quick, precise, energy efficient control of PAC demand. The results of experiments and case studies showed that the proposed method is 10% more energy efficient than the conventional intermittent operation method and has 4-5% accuracy for operating point control.

Marked T wave abnormalities in 12-lead electrocardiograms often appear after radiofrequency ablation in patients with Wolff-Parkinson-White (WPW) syndrome. Durations of the QRS complex before ablation have been reported to be significantly greater in patients with repolarization abnormalities after ablation than in those with normal repolarization. However, there has been no report concerning the relationship between QRS duration and repolarization abnormalities before ablation. It has been reported that QRST isointegral maps are dependent on local cellular repolarization properties but largely independent of activation sequence, and that they provide quantitative information about repolarization abnormalities. Isointegral maps were constructed from data recorded in 34 patients with WPW syndrome and QRS durations of 0.1 second or longer (21 patients with left-sided accessory pathways and 13 with right-sided pathways) in order to investigate the relationship between QRS duration and abnormalities in repolarization properties during preexcitation. Body surface ECGs were recorded with an 87-lead system at a sampling interval of 1 ms. The QRST values (mean +/- 2SD) from 607 normal individuals were taken to represent the normal range. The area with abnormally low QRST values was designated as the -2SD area and the sum of the QRST values (sigma QRST) in this area was calculated. The QRS duration was found to be significantly related to sigma QRST. These results demonstrate that the patients with WPW syndrome had abnormalities in local repolarization properties that were significantly related to QRS duration during preexcitation. The degree of preexcitation may be important in producing these abnormalities in patients with manifest WPW syndrome. This may result in T wave abnormalities after ablation of the accessory pathway attributable to cardiac memory.

Guinea pig skin becomes more pigmented following exposure to UV rays. This melanization was accompanied by enhanced intensity of tyrosinase-staining and increased number of tyrosinase-positive melanocytes (MELty+), with resultant enhancement of melanin synthesis. To clarify the regulatory mechanism for melanization following UV irradiation, organ-cultured guinea pig skins have been used to examine their melanogenic responses to exogenous stimulation. This organ culture system responded well to UV irradiation, by increasing melanogenic activity. Also, in this system, phospholipases (PL), arachidonic acid, interleukin-1 alpha and melanocyte-stimulating hormone, but not endothelin-1 or phosphatidylinositol-specific PLC (PI-PLC), stimulated melanogenesis to various extents as indicated by the number of MELty+ and morphological changes. Among them, the PLA2 and PLD were found to have a potent stimulatory property for melanocytes. They might affect melanocytes directly or indirectly through an effect on keratinocytes. These results suggest that PLA2 and PLD play a key role in epidermal hyperpigmentation after UV irradiation or inflammation.

31歳, 女性の恥丘部に生じた皮膚子宮内膜症の1例を報告した。右鼠径ヘルニア手術の既往あり。初診の半年前から右恥丘部に大豆大の皮下腫瘤が出現, 月経時に増強する圧痛を認めた。全摘生検術を実施し, 病理組織学的に子宮内膜症と診断した。成人女性の外陰部に皮下腫瘤をみた時には, 稀ではあるが本症も鑑別疾患に入れ, 月経に伴う症状を問診すべきである。

A 38-year-old woman complained of recurrent nodules on her anterior chest wall. She noticed the first nodule at the age of 12 and has since undergone surgical removal a total of 31 times. Finally, wide resection of parts of the rib cartilage and sternum and chest wall reconstruction were required. Histopathological examination of a series of surgical specimens were reevaluated. Immunohistochemical staining of the tumors by anti-CD34 antibody provided a definite diagnosis of dermatofibrosarcoma protuberans (DFSP). A noteworthy result was that her DFSP did not always express CD34; the recurrent tumors with myxoid and fibrosarcomatous changes lost their CD34 expression.

A 59-year-old woman with a large nodular ulcerative lesion on her neck was presented. She had a 3 year history of recurrent cutaneous nodules which spontaneously regressed before regional lymphadenopathies appeared. She has followed an indolent clinical course for seven years after the first overt lymphadenopathies appeared. Histological findings were compatible with anaplastic large cell lymphoma (ALCL). The tumor cells strongly expressed Ki-1 (CD30), HLA-DR, IL-2 receptor (CD25) and leukocyte common antigen. These findings led to the diagnosis of primary cutaneous Ki-1+ ALCL. Although the majority of the tumor cells did not express T-cell related antigens, the detection of monoclonal TCR gene rearrangement clearly established the T-cell lineage nature.

We investigated the usefulness of QRST isointegral maps (I-maps) for detecting posterior myocardial infarction (MI) with and without conduction disturbance. The I-maps were recorded during sinus rhythm and right ventricular (RV) pacing, which simulated left bundle-branch block (LBBB) in 19 patients with and in 20 patients without MI. Data on 608 normal subjects were used as controls. The "-2 SD area," where the QRST integral value was less than the lower limit of the normal range, was assessed by sigma DM (sum of QRST integral values below the normal range). Posterior MI was diagnosed with a sensitivity of 84%, a specificity of 90%, and a diagnostic accuracy of 87%, assuming that MI was present if sigma DM exceeded 50 mVms. During simulated LBBB, when the criterion sigma DM more than 250 mVms was used, the sensitivity, specificity, and diagnostic accuracy were 79, 75, and 77%, respectively. Thus, I-maps may be useful in detecting posterior MI in patients with and without an intraventricular conduction disturbance.

We investigated the use of the spatial ventricular gradient (VG) from vectorcardiogram (VCG) to determine whether significant repolarization differences were present in patients with WPW syndrome compared with normal subjects and also examined which VG parameter (i.e., elevation, azimuth, and magnitude) reflected the differences in repolarization properties during preexcitation. VG was calculated in 49 patients of Wolff-Parkinson-White (WPW) syndrome (group A: left-sided accessory pathway, n = 29; group B: right-sided, n = 20). Group N consisted of 607 normal subjects. In group A, the azimuth of VG was significantly (p < 0.01) greater than in groups B and N. In group B, the elevation of VG was significantly (p < 0.01) greater than in groups A and N. There were no significant differences in the magnitude of VG among groups. QRS duration was significantly (p < 0.01) related with the elevation of VG in group B. These findings suggested that VG is useful for spatial evaluation of repolarization abnormalities during preexcitation, which are related to the site of the accessory pathway.

A 50-year-old woman presented with a skin tumor on her right calf. The tumor had been noticed 20 years previously and grew to more than 60 mm in diameter. The histological findings were characterized by numerous bland xanthomatous histiocytes and a few atypical giant cells with pyknotic nuclei, although mitotic figures were few. These findings led to the diagnosis of dermatofibroma with unusual xanthomatous expression. Immunohistochemical studies using several markers for histiocytes (lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin and anti-CD68 antibody), anti-factor-XIIIa antibody and anti-CD34 antibody supported the diagnosis.

白血病児の点滴固定部に生じた皮膚アスペルギルス症の1例を報告した。患者は11歳の女児。9歳時に急性骨髄単球性白血病が発症し骨髄移植を受けたが再発, 化学療法施行中であった。点滴抜去時, 静注針固定用シーネが当たっていた右手掌小指球部に周囲に発赤·腫脹を伴う大豆大の壊死性潰瘍を認めた。鱗屑の苛性カリ直接鏡検でY字状に分岐する菌糸がみられ, 鱗屑および壊死組織の培養でAspergillus flavusが分離された。ポビドンヨード消毒とビフォナゾールクリームの外用1週間で略治した。病巣鱗屑の透過電顕観察では菌糸が角質細胞内に侵入している像がみられ, この菌がケラチナーゼを産生することを示唆する所見と考えた。1986年以降本邦で報告された原発性皮膚アスペルギルス症は自験例を含めて22例で, その過半数(12例)は白血病児の留置針固定部に生じた症例であった。原発性膿皮症様アスペルギルス症は5例であった。原因菌は留置針固定部に生じた症例では12例中10例でA. flavusであった。原発性膿皮症様アスペルギルス症の5例ではA. fumigatus2例, A. nigar2例, 両者の混合感染1例でありA. flavusによる症例はなかった。

Background. The most frequent radiation-induced skin cancers are basal cell carcinomas (BCCs), and in many cases, they may occur subsequent to tinea capitis, hypertrophic tonsillitis, acne vulgaris, atopic dermatitis, and hyperthyroidosis. BCCs occurring after radiotherapy for carcinoma of the cervix are extremely rare. Objective. To describe a case of multiple pigmented BCCs caused by radiotherapy for carcinoma of the cervix. Results. A 76-year-old female presented with four tumoral lesions within a previously irradiated area. The patient had undergone radiation therapy for cervical cancer 38 years before. All of the lesions were totally excised and histopathologically diagnosed as BCCs. There was no apparent gross chronic radiodermatitis around the lesions, but characteristic histopathologic alterations of radiodermatitis were observed. No new tumors were observed to date. Conclusion. The latent period for radiation-induced skin cancer is generally very long; secondary skin cancers can develop very late in life. Patients previously treated with radiation therapy require careful follow-up for life.

Background. Hidradenoma papilliferum is an uncommon benign tumor that is located almost exclusively in the vulvar and anal areas. It is usually very small and asymptomatic, and to make a correct diagnosis is clinically very difficult. Occasionally the tumor becomes elevated to form a reddish brown papillary mass, and the surface ulcerates, which may erroneously suggest malignancy. Objective. We report a case of a large, perianal hidradenoma papilliferum with suspected malignancy in a young Japanese female. Results. A 22-year-old female had been aware of a perianal nodule for approximately 1 year. Examination of the perianal area revealed a wide pedunculated, reddish nodule with several white maculae. It was ulcerated and bleeding, 2.0 × 1.2 × 0.8 cm in size, and located in the 3 o'clock position. The nodule was totally excised with a narrow margin. The histopathologic diagnosis was hidradenoma papilliferum. No recurrence was observed for 23 months. Conclusion. When dermatologists encounter tumors of the anogenital area of adult females, it is important to keep hidradenoma papilliferum in mind as the differential diagnosis. Dermatologists should recognize that the tumor is benign, eliminating the need for wide resection.

In the title compound, [Pt(C10H8N2)(C11H11N2)2](ClO4)4, the square-planar PtN4 coordination geometry is slightly deformed, with the coordinated N atom of one of the N-methyl-4,4′-bipyridinium (MQ) ligands 0.262 (8) A out of the plane defined by the rest of the coordinated N atoms and the Pt atom. The exceptional behavior of this MQ ligand is interpreted in terms of the electrostatic interactions between the positively charged MQ ligands and the perchlorate anions, where the N(MQ)⋯O(perchlorate) distances are in the range 2.932 (12)–3.259 (13) A.

Type 2 oculocutaneous albinism (OCA2) is an autosomal recessive disorder that results from mutations in the P gene that codes one of the melanosomal proteins, the function of which remains unknown. In this paper, we report the frequency of OCA2, 8%, among the Japanese albino population, six novel mutations containing four missense substitutions (P198L, P211L, R10W, M398I), and two splice site mutations (IVS15+1 G>A, IVS24-1 G>C). One of them, R10W, was within the putative signal peptide at the N-terminal of the P protein. This is the first report on the frequency of OCA2 in the Japanese albino population.

Accurate diagnosis of lymphoma includes the assessment of lineage-specific markers. Hematopoietic and lymphoid tissues express PAX5 exclusively in pro-B-cell to mature B-cell stages. However, some mature PAX5+ T-cell lymphomas have been reported. We report three cases of primary cutaneous CD30+ T-cell lymphoproliferative disorders (LPDs) with PAX5 expression: one cutaneous anaplastic large cell lymphoma (ALCL) and two cases of lymphomatoid papulosis (LyP). The three patients were 26 years old and female, 75 years old and female, and 65 years old and male. In all cases, Hodgkin's and Reed-Sternberg-like large lymphoid cells were present, positive for CD30, fascin, and PAX5, and negative for CD3, CD4, CD8, CD20, CD45RO, CD56, cytotoxic markers, and Epstein-Barr virus. The ALCL was accompanied by lymphadenopathy; the patient died of progressive disease 5 months after diagnosis. The LyP cases were localized in the skin with spontaneous regression. One case was diagnosed during pregnancy, transformed to ALCL, and ended in death 32 months after diagnosis despite multi-agent chemotherapy. This study is the first to address the clinical significance of PAX5+ primary cutaneous CD30+ T-cell LPDs. These cases were distinct regarding PAX5 expression and a relatively aggressive clinical course versus conventional primary cutaneous CD30+ T-cell LPDs.

We have cloned the cDNAs encoding tyrosinase-related protein-2 (TRP-2) from a human melanoma cDNA library. Transient expression of the isolated cDNA in HeLa cells established that TRP-2 is DOPAchrome tautomerase. Human TRP-2/DOPAchrome tautomerase is composed of 519 amino acids with a molecular weight of 59,000 and has about 84% identity with the mouse counterpart.

Background: Oculocutaneous albinism (OCA) is an autosomal-recessive genetic disorder defined by hypomelanosis in the eyes, hair, and skin. Piebaldism is an autosomal-dominant congenital leukoderma associated with a white forelock. The molecular pathogeneses of these congenital pigmentary disorders have been clarified in recent years and are briefly reviewed here. Observations: The pathologic gene mutations causing OCA and piebaldism are as follows. When a mutated tyrosinase gene produces inactive, less active, or temperature-sensitive tyrosinase, its phenotype is tyrosinase-negative (type I-A), yellow-mutant (type I-B), or temperature-sensitive (type I-TS) OCA, respectively. Mutation of the P gene encoding the tyrosine-transporting membrane protein probably occurs in tyrosinase-positive OCA (type II). A heterozygous mutation of the c-kit gene encoding mast cell-stem cell growth factor receptor induces piebaldism. Conclusion: The molecular bases of several types of OCA and piebaldism have been elucidated by gene technology, and other gene mutations causing OCA or many other pigmentary disorders will be clarified in the near future. (Arch Dermatol. 1994;130:355-358)

左上大静脈遺残, 心房中隔欠損症および肺静脈還流異常と診断された52歳の女性に, 動悸の精査を目的として心臓電気生理学的検査を施行したところ, 機序の異なる2種類のlongRP′頻拍 (SVTI, SVT2) が誘発された.SVT1は基本周期450msecの右室期外刺激法により誘発され, 頻拍周期は370msecで, 最早期心房興奮部位はヒス東電位図上の下位中隔右房であった.室房伝導曲線は減衰伝導を示した.頻拍中右室単一刺激法で, ヒス束の不応期に加えられた刺激が心房を捕捉したことにより, 前中隔部位に存在する減衰伝導性の“slowKent”束を経由する房室リエントリー性頻拍 (AVRT) と診断した.SVT2は右房連続刺激法により誘発され, 頻拍周期340mseGで, 最早期心房興奮部位は冠静脈洞入口部近位であった.頻拍中右室単一刺激はすべての連結期で頻拍をリセットしなかった.本例は二重房室結節伝導路を示し, SVT2の機序として稀有型房室結節リエントリー性頻拍が強く示唆されたが, 後中隔部位の“slowKent”束を介するAVRTの可能性は完全には否定し得なかった.

Eleven patients with squamous cell carcinoma (SCC) arising in burn scar, those were treated in Akita University hospital in these 21 years, are collected and discussed statistically. And two cases which resulted in death are detailed. Our data shows excellent survival rate after our treatment, i. e. 5-year survival rate of 7 patients of Stage-II was 100%.

This paper proposes the circuit configuration of a current-mode biquadratic filter which uses a pair of four-terminal active-current conveyors (CFCC II) consisting of a current follower attached to a second-generation current conveyor (CC II). the circuit is composed of one current adder and two current integrators. This configuration is capable of synthesizing arbitrary current-mode second-order transfer functions by changing the conditions (grounding or connecting) at the output terminals of the CFCC IIs. Each of the proposed filters has high output impedance so they can be cascaded directly. Moreover, ω0 and Q0 is determined from the ratio of passive elements, and the element sensitivity is even lower than 0.5. Since all the passive elements are grounded, this configuration is very advantageous to IC fabrication. Again, the effect of imperfection of CFCC II on the transfer function is studied and it is found that ω0 is influenced by the current conversion factor of CFCC II and Q0 is affected by the imperfection of the integrator. Moreover, it is shown that the operating frequency limits of the filter are determined by the permissible change of Q0. Each type of filter actually is synthesized, and the useful operation is confirmed by experiments.

Various microscopic classifications of metastatic sentinel lymph nodes (SLN) have been reported along with predictors of additional lymph node positivity and their correlations with the prognosis. The purpose of this study was to re-evaluate these classifications in the Japanese population. We selected the following three classifications, based on the procedural simplicity of the measurements: maximum diameter (maximum diameter of the largest tumor lesion in the SLN;0.1, 0.1-1.0,1.0 mm), invasion depth (depth of tumor invasion measured from the capsule in the SLN; SI ≤ 0.3 mm, SII0.3 to ≤ 1.0 mm, SIII1.0 mm), and microanatomic location (microanatomic location of the tumor deposits within the SLN; "subcapsular", "parenchymal", "combined", "multifocal", "extensive"). A retrospective study, using prescribed survey forms, was carried out. Among the 450 patients, including the 149 cases with SLN metastasis, an additional lymph node positivity rate of 0% could be predicted only in patients with a maximum diameter category of less than 0.1 mm. As compared with that in the SLN metastasis-negative cases, however, the prognosis was poorer in cases with SLN metastasis, even those with lesions falling under the maximum diameter category of less than 0.1 mm, invasion depth category of SI (≤ 0.3 mm) and microanatomic location category of subcapsular. The prognosis is particularly poor for the microanatomic location category of extensive, which should thus be regarded as a macrometastasis. A prospective study with standardized procedures, including pathological evaluation, is needed in order to confirm our conclusion.

Therapy-related myelodysplastic syndrome (t-MDS) is mostly attributed to chemotherapeutic agents of alkylating agents. Few studies have evaluated the late effects of chemotherapy for malignant melanoma (MM). To evaluate whether dacarbazine, nimustine hydrochloride and vincristine sulfate (DAV) therapy for MM related to t-MDS or not, a retrospective analysis was performed. We conducted a retrospective case-control study in a cohort of the 217 patients diagnosed with MM from 1989-2007 in Aichi Medical University Department of Dermatology and Nagoya University Graduate School of Medicine Department of Dermatology. One hundred and fifty-five of the 217 patients with MM were prospectively followed after DAV therapy or with or without local injection of β-interferon, of whom two patients developed t-MDS. Cytogenetic abnormalities were found in two of the 35 patients by chromosome banding method - leukemia (G-Banding). The karyotypes were found in the chromosome of -5, deletion (5), addition (7) and 7q-. In conclusion, DAV therapy should be used carefully for older patients with MM after satisfactory operation.

Since most first-generation antihistamines have undesirable sedative effects on the central nervous systems (CNS), newer (second-generation) antihistamines have been developed to improve patients’ quality of life. However, there are few reports that directly compare the antihistaminic efficacy and impairment of psychomotor functions. We designed a double-blind, placebo controlled, crossover study to concurrently compare the clinical effectiveness of promethazine, a first-generation antihistamine, and fexofenadine and olopatadine, second-generation antihistamines, by measuring their potency as peripheral inhibitors of histamine-induced wheal and flare. Further, we investigated their sedative effects on the CNS using a battery of psychomotor tests. When single therapeutic doses of fexofenadine (60 mg), olopatadine (5 mg) and promethazine (25 mg) were given in a double-blind manner to 24 healthy volunteers, all antihistamines produced a significant reduction in the wheal and flare responses induced by histamine. In the comparison among antihistamines, olopatadine showed a rapid inhibitory effect compared with fexofenadine and promethazine, and had a potent effect compared with promethazine. In a battery of psychomotor assessments using critical flicker fusion, choice reaction time, compensatory tracking, rapid visual information processing and a line analogue rating scale as a subjective assessment of sedation, promethazine significantly impaired psychomotor function. Fexofenadine and olopatadine had no significant effect in any of the psychomotor tests. Promethazine, fexofenadine and olopatadine did not affect behavioral activity, as measured by wrist actigraphy. These results suggest that olopatadine at a therapeutic dose has greater antihistaminergic activity than promethazine, and olopatadine and fexofenadine did not cause cognitive or psychomotor impairment.

While the incidence of malignant melanoma is much lower in Japanese than in Caucasians, the commonest site of melanoma in Japanese has been reported to be the acral regions of the limbs. The survival rate for acral and nodular melanoma observed at the Department of Dermatology, Tohoku University Hospital in Sendai, Japan from 1969 to 1990 was reviewed. Among 150 melanoma patients 125 (83%) and 17 (11%) had primary cutaneous melanoma and mucous membrane melanomas, respectively. Frequent sites for cutaneous melanomas were the sole (31%) and subungual regions (15%). Comparison of the stages of plantar melanoma at diagnosis showed that the proportion of stages III and IV decreased after 1980 with a corresponding increase in those with a tumour thickness of less than 4 mm (stage II). Concurrently, the prognosis of plantar melanoma has improved; the 5-year survival rate in each of the three periods 1969-75, 1976-80 and 1981-85 was 21, 70 and 90%, respectively. This was also the case with subungual melanoma. Such improvements in the prognosis are thought to be mainly due to early detection through the growing public awareness of this life-threatening disease. By contrast cases of nodular melanoma increased sharply after 1980. Among these, the high proportion of patients in advanced stages (stages III and IV) remained static even after 1980, with a resultant low 5-year survival rate in the above mentioned periods of 33, 38 and 18%, respectively.

QRST isointegral map (1-map) を用いて, 顕性WPW症候群における再分極特性の異常について検討した.顕性WPW症候群26例 (男性18例, 女性8例, 平均年齢38歳) , Rosenbaum分類A型16例, B型10例を対象とし, l-mapを記録, 正常対照608例と比較検討した.1-mapにおける極小はA型WPW症候群では全例で背部に, B型WPW症候群では右胸部中下部に (10例中6例) 位置した.A型の極小は対照のそれに比し有意に (p

This paper describes a circuit configuration for a biquad filter which utilizes the second-generation current conveyors (CC II) and is capable of synthesizing an arbitrary second-order transfer function. The circuit is composed of a subblock circuit with two positive CC IIs and a differential input circuit with two positive CC IIs. The subblock circuit realizes a lowpass, high-pass, and bandpass filter. Combining this with the differential input circuit produces an all-pass and notch filter. Each filter has a high input impedance because its input is the Y terminal of the CC II and can be cascaded without a buffer. The quality factor Q of the filter is determined by a ratio of passive elements, and its sensitivity to the passive element values is less than 0.5. These characteristics make the filters suitable for monolithic IC implementations. The effects of CC IIs voltage error ϵv and current error ϵi on the filter characteristics were studied. It was found that the center frequency ωo is independent of these errors, Q is affected only by ϵi, and the gain factor is a function of both ϵv and ϵi. Each filter was prototyped and was verified to operate as predicted.

62歳女性の右足底に生じたtumor thickness 1 mmの悪性黒色腫の1例を経験した。術前に行ったlymphoscintigraphyでは右鼠径と膝窩にsentinel nodeが存在すると考えられた。術中blue dyeを用いてsentinel node biopsyを行ったところ,右鼠径と膝窩にそれぞれ1個のsentinel nodeを認めた。これらには組織学的に転移は認められなかった。原発腫瘍が下腿以下にある場合sentinel nodeは膝窩にも存在することもあり,術前にlymphoscintigraphyを行いsentinel nodeの位置を確認する必要があると思われた。

Interval sentinel lymph nodes (ISLN) are defined as the lymph nodes located between the primary melanoma and anatomically well-defined lymph nodal basins. It was reported that the ISLN appeared to be at the same metastatic risk as sentinel lymph nodes (SLN) in the traditional nodal basins. This study aimed to examine the incidence and metastatic risk of the ISLN in melanoma patients. Between June of 1999 and December of 2008, 117 patients enrolled at Nagoya University Hospital underwent SLN biopsy for primary cutaneous melanoma with a Breslow thickness of at least 1.0 mm. Triple techniques with lymphoscintigraphy, blue dye injection and gamma probe were used for the biopsy except for 13 cases that underwent lymphoscintigraphy, ultrasonography and blue dye injection, but without gamma probe. Patients who had melanoma of the head and neck were excluded from this analysis. The SLN were identified in 253 nodal basins from 117 patients, and ISLN were found in six patients (5%). We recognized 41 (17%) SLN metastases in 246 conventional nodal basins and one (14%) in seven ISLN. Although ISLN were identified infrequently, the incidence of metastasis into the ISLN was similar to that into SLN in conventional nodal basins. It is therefore recommended that preoperative lymphoscintigraphy and intraoperative recognition of ISLN should be performed.

Lens epithelium-derived growth factor (LEDGF)/dense fine speckles 70 kDa protein (DFS70) is a transcription cofactor that enhances growth and is overexpressed in various cancers. In the epidermis, LEDGF/DFS70 localizes to the nucleus of keratinocytes (KCs) in the basal layers and to the cytoplasm of cells in the upper layers. However, the biological and pathological relevance of LEDGF/DFS70 in the epidermis is virtually unknown. Compared with normal epidermis, we detected strong nuclear staining of LEDGF/DFS70 in both the spinous and basal layers of the epidermis of psoriatic skin. To investigate the roles of LEDGF/DFS70 in the epidermis of psoriatic skin, we generated HaCaT cells that constitutively express enhanced green fluorescence protein (EGFP)-LEDGF (EGFP-LEDGF-HaCaT) or EGFP alone (EGFP-HaCaT) as a control. EGFP-LEDGF-HaCaT cells had increased expression of IL-6, which was attenuated by LEDGF-specific RNA interference and the p38-specific inhibitors SB-239063 and SB-203580. Furthermore, EGFP-LEDGF-HaCaT cells had increased expression of S100A7 and S100A9 and decreased expression of filaggrin. These findings are compatible with the expression pattern in psoriatic tissues. Taken together, these results strongly suggest that ectopic expression of LEDGF/DFS70 in KCs could be involved in the pathology of psoriasis vulgaris.

Epidermal growth factor receptor tyrosine kinase (EGFR-TK) is a transducer of mitogenic signals, and is involved in the pathogenesis and progression of a number of cancers, including non-small cell lung cancer (NSCLC). Gefitinib is an EGFR-TK inhibitor that is clinically used to treat NSCLC; however, this drug frequently causes adverse effects, including skin eruptions. The mechanism underlying these skin reactions is elusive, although it is assumed that they are caused by the inhibition of EGFR-TK signalling in epidermal and adnexal cells. In this article, we demonstrate by immunocytochemistry that the skin lesions of patients treated with oral gefitinib had higher expression of CCL2 and CCL5 compared to normal human epidermis. Further, PD153035, a gefitinib prototype, induced CCL2 and CCL5 mRNA and protein expression in HaCaT and HSC-1 keratinocyte cell lines with or without interleukin-1 (IL-1) treatment in vitro. PD153035 also reduced the levels of interleukin-1 receptor 2 (IL-1R2), an IL-1 decoy receptor. Moreover, we demonstrate that reduction in IL-1R2 by RNA interference increased IL-1-mediated CCL2 and CCL5 mRNA and protein expression. Taken together, our data strongly suggest that IL-1-mediated signalling is activated to induce the high expression of CCL2 and CCL5 via reduction in IL-1R2 in the skin lesions caused by gefitinib.

Psoriasis vulgaris is a chronic inflammatory disorder of the skin, in which activation of keratinocytes and crosstalk between keratinocytes and T cells or dendritic cells are considered to be involved in the pathogenesis of psoriasis vulgaris. Cyclosporin (Cy) A, an immunomodulator, has been used for the treatment of psoriasis vulgaris, but the mechanism of its action on keratinocytes has not been well elucidated as its function on T cells is well known. Previous study indicated that the expression of the unfolded protein response (UPR) markers, GRP78/Bip and HRD1 were poorly expressed in psoriasis vulgaris. To investigate if the UPR in keratinocytes is involved in the pathogenesis of psoriasis vulgaris we assessed immunocytochemistry of normal human skin and psoriatic lesions, quantitative PCR of keratinocyte cell line (HaCaT) treated with TGFβ. Moreover, to elucidate how CyA effects on the UPR in keratinocytes, we set out quantitative PCR and western blotting, HaCaT and squamous cell carcinoma cell lines (HSC-1) treated with CyA and CyA analog, cyclosporin D. Furthermore, the siRNA-mediated knockdown effect of cyclophilin (Cyp) A, Cyp B and Cyp C on HaCaT cells were also examined. As a result, the UPR was downregulated in keratinocytes from psoriatic lesions, characterized by immunocytochemical staining of GRP78/Bip, CHOP/GADD153, HRD1 and C/EBPβ. TGFβ induced UPR markers in HaCaT cells. CyA treatment and siRNA-mediated knockdown of Cyp B induced the UPR in HaCaT cells or HSC-1 cells. Altogether, we demonstrate that in psoriasis vulgaris CyA or reduction in Cyp B by RNA interference might induce the UPR in keratinocytes.

Objectives. Myositis-specific autoantibodies are useful for diagnosing PM/DM. Recently, two new myositis-specific autoantibodies against melanoma differentiation-associated gene 5 (MDA5) and transcriptional intermediary factor 1-g (TIF1-g) were identified in DM. Here, we detected these autoantibodies in patient sera using new assays with recombinant MDA5 and TIF1-g, and associated clinical features with the presence of anti-MDA5 or anti-TIF1-g antibodies. Methods. We screened 135 Japanese patients with various CTDs, including 82 with DM. DM patients were classified as clinically amyopathic DM (CADM), cancer-associated DM or classical DM without cancer. Anti-MDA5 and anti-TIF1-g antibodies were detected by their ability to immunoprecipitate biotinylated recombinant proteins. Results. Sera from 21 (26%) of 82 DM patients immunoprecipitated MDA5, and every anti-MDA5-positive patient had DM (except one patient with SSc). Sera from 20 (65%) of 31 CADM patients reacted with MDA5. Notably, anti-MDA5-positive DM patients had significantly more interstitial lung disease than anti-MDA5-negative DM patients (95 vs 32%, P < 0.001). Sera from 12 (15%) of 82 DM patients immunoprecipitated TIF1-g, and anti-TIF1-g antibodies were only detected in DM patients. Strikingly, 7 (58%) of 12 patients with cancer-associated DM had sera that reacted with TIF1-g. Anti-TIF1-g-positive DM patients had significantly more internal malignancies than anti-TIF1-g-negative DM patients (58 vs 9%, P < 0.001). Conclusions. Anti-MDA5 and anti-TIF1-g antibodies were confirmed to be serological DM subset markers. Anti-MDA5 and anti-TIF1-g antibodies were detected based on their ability to immunoprecipitate biotinylated recombinant MDA5 and TIF1-g, and were closely associated with life-threatening complications in DM.

Assessment of sentinel lymph node status is commonly performed in the treatment of cutaneous melanoma. However, there are no definite guidelines for thin melanomas with Breslow tumor thickness1.0 mm, in part because thin melanomas are relatively infrequently positive for lymph node metastasis.We analyzed the clinicopathologic relationship among tumor thickness, mitotic index, tumor infiltrating lymphocytes (TIL), tumor size, regional lymph node metastasis and prognosis in 66 Japanese patients with thin melanomas. Immunohistochemical evaluations for TIL were also performed.Thirty-one of the 66 melanomas were Clark level I without lymph node metastasis (0/31, 0%). In tumors of Clark level II or higher (35/66), there were five (14%) regional lymph node metastasis. Melanomas with two or more mitoses in 1 mm(2) per high-power fields showed higher frequencies of lymph node metastasis (2/3, 67%), compared to those with fewer than two mitoses (3/32, 9%). Tumors with intensive TIL that partially or completely surrounded the tumor revealed higher frequencies of lymph node metastasis (5/28, 18%), compared to those with none or slight TIL (0/7, 0%). The main components of TIL were CD8-positive T lymphocytes. No metastasized tumors were under 2.0 cm(2) .The presence of mitotic activity, large tumor size and an intense lymphocytic infiltrate should prompt sentinel lymph node biopsy in thin melanomas.

Normal human epidermal melanocytes became swollen and more dendritic with an increase in the amount of tyrosinase and immunoreactive b-locus protein when they were cultured for 2 days with the following arachidonic acid metabolites: prostaglandin (PG) D2, leukotriene (LT) B4, LTC4, LTD4, LTE4, thromboxane (TX) B2 and 12-hydroxy eicosatetraenoic acid (12-HETE). The effect of LTC4 was particularly strong compared to that of PGE2, about which we have previously reported. On the other hand, PGE1, PGF2 alpha and 6-ketoPGF1 alpha did not show any significant stimulatory effect. These data suggest that arachidonate-derived chemical mediators, especially LTC4, may be responsible for the induction of post-inflammatory hyperpigmentation of the skin.

The effects of right ventricular pacing, which simulated left bundle branch block (BBB), on QRST time-integral values of 12-lead electrocardiograms (ECGs) were examined, and the clinical usefulness of QRST values for estimating the severity of left ventricular wall motion abnormalities due to a prior anterior wall myocardial infarction (MI) in the setting of left BBB were evaluated. Digitized ECGs were recorded during normal sinus rhythm and simulated left BBB in 38 patients (24 with and 14 without prior anterior wall MI). QRST values were calculated in each lead point of 12-lead ECGs. Data from 608 normal subjects were used as control values; the mean +/- 2 SD of these values was regarded as the normal range. The parameter sigma DE was defined as the sum of the differences between the normal mean QRST value and the QRST values of a given patient in leads where the QRST value was less than the normal range. The correlation coefficient of sigma DE for the 2 activation sequences was highly significant. Although small but significant changes were seen in QRST values in leads I, II, III, aVR, aVF and V1 during simulated left BBB, left precordial leads showed no significant changes in QRST values. A criterion of sigma DE > 40 mV.ms for detecting an anterior wall MI showed a sensitivity of 88%, a specificity of 93%, and a diagnostic accuracy of 89%. The sigma DE was significantly (p < 0.001) correlated with the asynergy index calculated from left ventriculograms.(ABSTRACT TRUNCATED AT 250 WORDS)

To identify the cis-acting element that is responsible for the pigment cell-specific expression of the human tyrosinase gene, we analyzed the promoter activity of its 5'-flanking region by transient expression assays. The fusion genes were constructed by inserting the 5'-flanking region of the human tyrosinase gene upstream from the firefly luciferase gene and were introduced into human melanoma cells and HeLa cells. We thus found the element, located between 2.7 and 1.8 kilobase pairs upstream from the transcription initiation site, that enhances the transient expression of the luciferase reporter gene in melanoma cells, but not in HeLa cells, the tyrosinase gene expression of which is not detectable. Using the fusion genes containing putative enhancer elements under the control of the heterologous simian virus 40 promoter, we identified the pigment cell-specific enhancer of approximately 200 base pairs (bp) between -2.0 and -1.8 kilobase pairs and localized the core sequence to a 39-bp region. This 39-bp core element was then confirmed to direct the melanoma cell-specific expression of the reporter gene under the tyrosinase gene promoter. We thus propose that this core element is responsible for the pigment cell-specific expression of the human tyrosinase gene.

The clinical usefulness of QRST isointegral maps for assessing left ventricular (LV) dysfunction due to myocardial infarction (MI) in patients with MI in the setting of simulated left bundle branch block (LBBB) was investigated. Isointegral maps were recorded during sinus rhythm and right ventricular pacing, which simulated LBBB, in 62 patients with MI and 26 patients without MI. An abnormal decrease in the QRST value in the isointegral map was assessed by the difference map that indicated a "-2 SD area" where the QRST integral value was less than the normal range (mean - 2 SD) calculated from 608 normal individuals. The isointegral maps during the two activation sequences were similar in patients with and without MI (r = 0.87 and 0.92, respectively). The sum of QRST integral values less than the normal range (sigma DM) during simulated LBBB correlated significantly with the asynergy index, derived from left ventriculographic data (r = 0.81, p0.01). LV dysfunction (asynergy indexor = 2) was diagnosed in simulated LBBB with a sensitivity of 81%, specificity of 77%, and diagnostic accuracy of 80% when the criterion that LV dysfunction is present if the number of lead points in the -2 SD area exceeds 4, and a sensitivity of 71%, specificity of 81%, and diagnostic accuracy of 74% if sigma DM exceeds 200 mVms was used. The findings demonstrate that isointegral maps may be useful in assessing LV dysfunction due to MI in patients with MI and LBBB in addition to detecting the presence and site of MI in these patients.

冠動脈造影, 左室造影を施行した38症例 (陳旧性前壁梗塞24例, 非梗塞例14例) において右室ペーシングにより左脚ブロックを模し, その際体表面電位図 (MAP) , 12誘導心電図 (EOG) およびベクトル心電図 (VOG) を同時記録し, これら3者におけるQRST値の心筋梗塞診断, および左室機能の推定について比較検討した.MAPおよびEOGにおいては, 正常範囲を下回る誘導のQRST値と正常平均との差の総和 (ΣDMおよびΣDE) を, VCGについてはVentricular gradient (VG) のAzimuth (AZM) , Elevation (ELE) , Magnitude (MAG) を算出した.ΣDMとΣDEおよびAZM, ELEとMAGは陳旧性前壁梗塞において正常興奮伝播と右室ペーシングにより模した左脚ブロックとの間で有意な相関を認めた.陳旧性前壁梗塞の有無の診断におけるMAP, ECGおよびVCGの正診率はそれぞれ82%, 89%および79%であった.右室ペーシング時のΣDM, ΣDEおよびAZMはAsynergy Indexと有意な相関を示したが, ΣDMの相関が最も優れていた.MAP, ECGおよびVCGのQRST値から得られた指標は, 左脚ブロックに合併した前壁心筋梗塞の有無および左室機能の推定に有用な情報を提供する可能性が示唆された.

To investigate the prevalence of anti-ribosomal P protein (anti-P) antibodies in Japanese patients with connective tissue diseases (CTDs) using enzyme-linked immunosorbent assays (ELISAs) and western blotting (WB) and to evaluate the indirect immunofluorescence (IIF) staining patterns of anti-P-positive sera.Anti-P antibodies were measured by two different commercially available ELISA kits and WB in 239 outpatients, 99 with systemic sclerosis (SSc), 73 with systemic lupus erythematosus (SLE), 45 with dermatomyositis (DM), and 22 with Sjögren's syndrome (SjS). Sera positive for anti-P antibodies by WB were analysed by IIF.The frequency of positive WB findings in SLE (18/73, 25%) was higher than in other diseases. ELISA kits A and B for anti-P antibodies showed 21% and 43% sensitivity, and 93% and 88% specificity, respectively, for diagnosing SLE, based on the manufacturer's cut-off values. Receiver operating characteristic (ROC) curve analysis, based on positive WB findings, determined a new cut-off threshold but revealed that both ELISA kits still had good diagnostic characteristics. In IIF assays on anti-P antibody positive sera, typical anti-P antibody cytoplasmic staining patterns (n=8) were seen less frequently than other staining patterns (n=17).Routine screening for anti-P antibodies by IIF has low sensitivity. ELISAs using cut-off values established by individual facilities are suitable for detecting anti-P antibodies and provide a tool with good diagnostic characteristics, on a parity with WB.