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We previously reported liver stiffness (LS) as a prognostic predictor of portosystemic shunt (PSS) occlusion. This study aims to reinvestigate the predictive factors of the model for end-stage liver disease-sodium (MELD-Na) score amelioration following balloon-occluded retrograde transvenous obliteration (BRTO) and to evaluate the postoperative prognoses of patients with portal hypertension by using newly identified factors.Seventy-five patients who underwent BRTO between 2008 and 2021 were retrospectively enrolled. The MELD-Na scores were calculated preoperatively and one month postoperatively. We monitored long-term outcomes and analyzed postoperative survival.At one month postoperatively, the MELD-Na score decreased in 46 (61.3%) patients. Univariate analyses revealed a significant association of the score amelioration with nine factors, including lower LS levels and a higher international normalized ratio (INR). A multivariate logistic regression analysis with receiver operating characteristic curve analyses identified preoperative LS levels and INR as significant independent predictors of the postoperative MELD-Na score amelioration, with optimal cutoffs of 28.1 kPa and 1.06, respectively. The combination of LS 28.1 kPa and INR ≥ 1.06 showed a sensitivity and specificity of 84.8% and 75.9% for the prediction of the score amelioration, respectively. For the propensity score model, we matched 24 patients with similar age, sex, MELD-Na score, and concomitant hepatocellular carcinoma. Kaplan-Meier analysis determined significantly higher cumulative survival rates in patients with LS 28.1 kPa and INR ≥ 1.06 than in other populations.A combination of LS and INR can predict the MELD-Na score amelioration and prognosis improvement following PSS occlusion.

Despite the promising efficacy of atezolizumab plus bevacizumab (atezo/bev), some patients with unresectable hepatocellular carcinoma (HCC) experience disease progression. This retrospective study, which included 154 patients, aimed to evaluate predictors of treatment efficacy of atezo/bev for unresectable HCC. Factors associated with treatment response were examined, focusing on tumor markers. In the high-alpha-fetoprotein (AFP) group (baseline AFP ≥ 20 ng/mL), a decrease in AFP level > 30% was an independent predictor of objective response (odds ratio, 5.517; p = 0.0032). In the low-AFP group (baseline AFP < 20 ng/mL), baseline des-gamma-carboxy prothrombin (DCP) level < 40 mAU/mL was an independent predictor of objective response (odds ratio, 3.978; p = 0.0206). The independent predictors of early progressive disease were an increase in AFP level ≥ 30% at 3 weeks (odds ratio, 4.077; p = 0.0264) and the presence of extrahepatic spread (odds ratio, 3.682; p = 0.0337) in the high-AFP group and up-to-seven criteria, OUT (odds ratio, 15.756; p = 0.0257) in the low-AFP group. In atezo/bev therapy, focusing on early AFP changes, baseline DCP, and tumor burden of up-to-seven criteria are useful in predicting response to treatment.

Recent success of systemic therapeutic agents, including combination immunotherapy, could promote a change in the treatment strategy in patients with advanced hepatocellular carcinoma (HCC). Although hepatic arterial infusion chemotherapy (HAIC) is a treatment option for advanced HCC in Japan, it is not recommended by other guidelines. We discuss the clinical benefits of HAIC compared to sorafenib. The clinical benefits of HAIC are as follows: (1) even a patient with Child–Pugh B HCC (7 or 8 points) is a candidate for HAIC (2) Child–Pugh scores barely decline with the use of HAIC compared with sorafenib (3) HAIC is highly effective in patients with vascular invasion compared with sorafenib; and (4) survival in patients receiving HAIC may not be associated with skeletal muscle volume. In contrast, the disadvantages are problems related with the reservoir system. HAIC has clinical benefits in a subpopulation of patients without extrahepatic metastasis with Child–Pugh A HCC and vascular invasion (especially primary branch invasion or main portal vein invasion) or with Child–Pugh B HCC.

Chronic liver diseases, including hepatocellular carcinoma (HCC), lead to an imbalance in energy metabolism. The non-protein respiratory quotient (npRQ), which estimates energy malnutrition, can be evaluated using an indirect calorimeter; however, npRQ measurement is limited in routine work. This study aimed to investigate the relationship between the albumin-bilirubin (ALBI) score and npRQ in patients with HCC.We conducted a retrospective cohort study in 109 patients with HCC who underwent indirect calorimetry and then compared the npRQ with various clinical parameters, including liver function and tumor factors.The median npRQ was 0.82. A significant negative correlation was found between the npRQ and the ALBI score (r = -0.35, p 0.001). The median npRQ in modified ALBI (mALBI) grades 1, 2a, 2b, and 3 were 0.84, 0.86, 0.81, and 0.79, respectively (grade 2a vs. 2b, p = 0.002). Factors associated with npRQ0.85, which is reported to be the best cutoff value for energy malnutrition, were analyzed. On multivariate analysis, the ALBI score (cutoff value, -2.18) was the only significant independent factor (odds ratio, 7.65; p 0.001). The proportion of HCC patients with npRQ0.85 significantly increased among patients with an ALBI score ≥-2.18 (45/51, 88.2%) compared with those with an ALBI score-2.18 (29/58, 50%) (p 0.001).The ALBI score might be a useful predictor for energy malnutrition in patients with HCC. In addition, most HCC patients with mALBI grade 2b or 3 can be considered to have energy malnutrition.

There are limited reports regarding early predictors of objective response (OR) in patients with hepatocellular carcinoma (HCC) treated with lenvatinib. This retrospective study including 70 patients aimed to investigate the efficacy of hepatic biochemical markers. Changes in tumor marker (alpha-fetoprotein (AFP)/des-gamma-carboxy prothrombin (DCP)) levels and albumin&ndash, bilirubin (ALBI) score between the baseline value and that estimated one month after treatment were evaluated. We identified several predictors of OR, including changes in tumor marker levels. The OR rate calculated using modified Response Evaluation Criteria in Solid Tumor (mRECIST) was 41.4%. Response was defined as a reduction in AFP and DCP levels of &ge, 40% from baseline. OR was significantly associated with AFP response, but not with DCP. Predictors of OR were evaluated in two groups (high-AFP group: baseline AFP &ge, 10 ng/mL, low-AFP group: remaining patients). A multivariate analysis identified AFP response (odds ratio, 51.389, p = 0.001) and ALBI score (odds ratio, 6.866, p = 0.039) as independent predictors of OR in the high-AFP and low-AFP groups, respectively. Changes in the ALBI score indicated deterioration in both responders and non-responders, with a significant difference in non-responders (p = 0.003). AFP response, baseline ALBI score, and change in the ALBI score were early predictors of OR in patients with HCC undergoing lenvatinib treatment.

Previous studies have reported prognostic factors for hepatocellular carcinoma (HCC) patients receiving lenvatinib, however, no studies have evaluated the effects of both handgrip strength and skeletal muscle mass on the clinical outcomes. Therefore, this retrospective study investigated the individual effect of handgrip strength, skeletal muscle mass, and sarcopenia on clinical outcomes of 53 HCC patients treated with lenvatinib. Before receiving lenvatinib, handgrip strength and skeletal muscle index (SMI) were measured. Low handgrip strength and muscle depletion were defined as &lt, 26 and &lt, 18 kg and SMI &lt, 42 and SMI &lt, 38 cm2/m2 in men and women, respectively. Sarcopenia was defined as having low handgrip strength and muscle depletion. Multivariate analysis identified modified albumin&ndash, bilirubin grade 1&ndash, 2a (p = 0.010), Barcelona Clinic Liver Cancer stage A&ndash, B (p = 0.011), and absence of low handgrip strength (p = 0.015) as favorable prognostic factors for survival. Furthermore, sarcopenia was an independent significant prognostic factor for survival. Time to treatment failure was associated with handgrip strength and sarcopenia. Our findings suggest that handgrip strength may be a useful marker of clinical outcomes in HCC patients treated with lenvatinib.

Patients with dermatomyositis positive for anti-aminoacyl tRNA synthetase (ARS) antibodies, also known as antisynthetase syndrome (ASS), frequently present with mechanic's hand and interstitial lung disease (ILD). We first screened the antibody profiles of 59 patients with dermatomyositis, and then examined the cutaneous, muscular and pulmonary manifestations characteristic for patients with ASS. The anti-ARS antibodies Jo-1, PL-7, PL-12, EJ and KS, along with antibodies to TIF1-γ, MDA5 and Mi-2, were examined. Among the 59 patients, 20, 21, 15 and three patients were classified into the ASS, non-ASS, myositis-specific antibody-negative and unknown groups, respectively. Five of 16 patients (31%) with ASS had six relatives with a history of collagen diseases, within the second degree of relationship, including two cases of dermatomyositis (vs the non-ASS group, P = 0.018). Patients with ASS more frequently presented with fever and arthralgia, and had elevated levels of C-reactive protein. Nine of the 11 finger lesions (82%) clinically diagnosed as mechanic's hands showed a psoriasiform tissue reaction. ILD was observed in 19 of 20 patients (95%) with ASS, and eight of 21 patients (38%) in the non-ASS group, in which six patients possessed anti-MDA5 antibody. Patients with ASS showed higher serum levels of muscle enzymes, and four of 12 patients (33%) had fasciitis-dominant myopathy, while only one of 11 patients (9%) in the non-ASS group had fasciitis-dominant myopathy. Patients with ASS often present with a psoriasiform tissue reaction in the hand lesions and fasciitis-dominant myopathy, and the relatives of those with ASS are at high risk for collagen diseases.

Aim Insulin resistance (IR) increases during the early stages of hepatitis C virus (HCV)-related chronic liver disease and is a sign of poor prognosis as well as a risk factor for hepatic fibrosis and hepatocellular carcinoma. We aimed to determine the factors affecting IR in HCV-related chronic liver disease. Methods We retrospectively examined 71 patients with HCV-related chronic liver disease and analyzed various parameters, including amino acids, as possible predictors of IR. IR was assessed using the Homeostasis Model of Assessment – Insulin Resistance (HOMA-IR). Amino acids were assayed by examining branched-chain amino acids (BCAA), tyrosine level, and the ratio of BCAA to tyrosine level (BTR). Results HOMA-IR was significantly correlated with body mass index, platelet count, prothrombin time, hemoglobin, total bilirubin, total protein, albumin, total cholesterol, fasting glucose, BTR (r = −0.46, P = 0.0001) and tyrosine (r = 0.55, P

A 67-year-old woman who underwent left breast mastectomy and right breast partial mastectomy under the diagnosis of left breast cancer and suspected right breast cancer 10 years earlier was admitted because of dyspnea. Chest computed tomography revealed pericardial fluid accumulation. The patient was treated with pericardial drainage; thereby, 800 mL of bloody fluid was removed. The cytological diagnosis was malignancy. After receiving mitomycin C instillation, she underwent systemic chemotherapy and endocrine therapy. At the last follow-up more than 5 years after the recurrence, no reaccumulation of the pericardial fluid was observed, and she remained alive in good condition.

Summary Staphylococcal infections cause a variety of cutaneous and systemic infections, including impetigo, furuncle, subcutaneous abscess, staphylococcal scalded skin syndrome (SSSS), toxic shock syndrome (TSS) and neonatal toxic shock syndrome-like exanthematous disease (NTED), in association with microbial virulence factors. The virulence factors produced by Staphylococcus aureus have a wide array of biological properties, including disruption of the epithelial barrier, inhibition of opsonization by antibody and complement, interference with neutrophil chemotaxis, cytolysis of neutrophils, and inactivation of antimicrobial peptides. Exfoliative toxins (ETs) induce the ‘acantholytic’ infection of S. aureus due to the disruption of cell-to-cell cohesion, which allows the pathogenic organisms to spread within the epithelium. Furthermore, S. aureus expresses exotoxins with biological properties of superantigens that induce T-cell activation with subsequent anergy and immunosuppression. Of the S. aureus leukotoxins, Panton-Valentine leukocidin (PVL) is involved in the development of multiple furuncles with more intense erythema, particularly in healthy young adults. TSS is an acute life-threatening illness caused by TSS toxin-1 (TSST-1) and is usually classified into two categories; menstrual TSS, originally described in association with tampon use, and nonmenstrual TSS with a variety of clinical settings. NTED is a neonatal disease induced by TSST-1 although clinical symptoms are much milder than those of TSS. In TSS and NTED, the expansion of TSST-1-reactive Vβ2-positive T cells is observed. The production of pathogenic S. aureus exotoxins and biofilm formation is regulated by the accessory gene regulator (agr) locus in the quorum-sensing signaling pathway. There is no doubt that targeting the quorum-sensing signaling pathway or anti-toxin therapy is a promising therapeutic approach supportive of primary antibiotic therapy.

Summary Background Granulysin is a recently identified antimicrobial protein expressed on cytotoxic T cells, natural killer (NK) cells and NKT cells. It has been shown that granulysin contributes to the defence mechanisms against mycobacterial infection. Superficial microbial folliculitis is a common skin disease. In a previous report, we showed that, as a first line of defence, α-defensin, a human neutrophil peptide, and β-defensin (human β-defensin-2) were expressed in infiltrating neutrophils and in lesional epidermal keratinocytes, respectively, in superficial folliculitis. As we also observed many infiltrating lymphocytes in lesional dermis, we hypothesized that infiltrating lymphocytes may possess antimicrobial substances, such as granulysin, and play a role in the defence mechanism as a second line of defence. Objectives Seven specimens of superficial microbial folliculitis diagnosed clinically and histologically were examined by means of immunohistochemistry. To identify the phenotype of cells expressing granulysin, confocal laser microscopic examination was performed. Results A dense lymphoid cell infiltrate was observed in pustules, in the perivascular regions. A large number of these lymphoid cells were positive for granulysin. Phenotypically, cells consisted of CD3+ T cells, CD8+ T cells and UCHL-1+ T cells. CD20+ cells and CD56+ cells were not observed. Microscopic examination with a confocal laser showed that the lymphocytes producing granulysin were CD3+ and CD4+ T cells but not CD8+ T cells. Conclusions We showed that many granulysin-bearing T cells infiltrated affected follicles and perilesional dermis in superficial microbial folliculitis. However, few granulysin-positive lymphoid cells were observed in sterile pustular lesions. Our observations indicated that adaptive immunity such as granulysin, a lymphocyte-produced antimicrobial protein, may play an important role in the cutaneous defence mechanism.

症例は52歳男性. 1999年著明な黄疸, 肝機能障害にて入院しB型肝炎ウイルスキャリアよりの劇症肝炎と診断された. 入院後血漿交換, 血液濾過透析などのアフェレーシス, およびステロイドの大量療法により救命に成功した. しかし, 治療終了後, ステロイドの免疫抑制によりB型肝炎ウイルスが増殖し, これによる肝炎の再燃が認められた. 肝炎の改善にはウイルス量を減らす必要があると考えB型肝炎ウイルスに対する新たな抗ウイルス薬として認可されたラミブジンを投与したところ, ウイルス量は著減し肝機能も改善がみられた. 劇症肝炎は予後が極めて不良で救命率は30%前後に過ぎないため治療的アフェレーシス, 免疫抑制療法による救命が最優先される. 救命後, 免疫抑制剤によるウイルス増殖に起因した肝炎の再燃が問題となるが, ラミブジンはこの肝炎の再燃に極めて有効であった.

SummaryBackground Glycocalyx collapses during dehydration to produce electron-dense accretions. Confocal laser scanning microscopy (CLSM) may be used to visualize fully hydrated microbial biofilms. Objectives Using CLSM, to analyse glycocalyx production by Staphylococcus aureus cells in skin lesions of bullous impetigo, atopic dermatitis and pemphigus foliaceus. A second objective was to compare numbers of S. aureus cells in tissue sections prepared by different methods for routine light microscopy. Methods S. aureus cells in skin lesions of impetigo, atopic dermatitis and pemphigus were stained with safranin, and positive staining with fluorescein isothiocyanate-conjugated concanavalin A was considered to indicate the presence of glycocalyx. Results All S. aureus cells tested in skin lesions of impetigo, atopic dermatitis and pemphigus were covered with glycocalyx and formed microcolonies. The numbers of S. aureus cells in a routine light microscopy section were significantly lower than those in a frozen section that had not been dehydrated with ethanol. Conclusions S. aureus cells generally produce glycocalyx in skin lesions of bullous impetigo, atopic dermatitis and pemphigus foliaceus, which accounts for the difficulty of removing S. aureus cells from these skin lesions. The glycocalyx may collapse during dehydration and most of the S. aureus cells may be carried away during preparation of routine light microscope sections.

SummaryBackground Bacteria that adhere to damaged tissues encase themselves in a hydrated matrix of polysaccharides, forming a slimy layer known as a biofilm. This is the first report of detection of glycocalyx production by Staphylococcus aureus using confocal laser scanning microscopy (CLSM) on damaged skin tissues. Objectives To analyse glycocalyx production by S. aureus cells on damaged skin tissues and the influence of polymorphonuclear leucocytes (PMNs) and various antimicrobial agents on its production using CLSM in cyclophosphamide (Cy)-treated (neutropenic) or non-Cy-treated (normal) mice. Methods S. aureus cells were inoculated on damaged skin tissues in neutropenic or normal mice with or without topical application of antimicrobial agents. S. aureus cells were stained with safranine, and positive staining with fluorescein isothiocyanate-conjugated concanavalin A was considered to indicate the presence of glycocalyx. Results All S. aureus cells tested on damaged skin tissues formed microcolonies encircled by glycocalyx. The colony counts of S. aureus cells on croton oil dermatitis in normal mice treated with 2% fusidic acid ointment were about 100 times lower than those in neutropenic mice (control). Conclusions As S. aureus cells can generally produce a biofilm on damaged skin tissues, antimicrobial agents may not eradicate S. aureus cells without the help of PMNs. S. aureus glycocalyx may play a crucial role in colonization and adherence to damaged skin tissues.

Human neutrophil peptide-1 (HNP-1), a defensin with antimicrobial properties, is also thought to promote wound healing. To elucidate the mechanism by which wound healing is facilitated by this factor, we investigated the effect of HNP-1 on the expression of interstitial collagenase (matrix metalloproteinase 1, MMP-1), collagen types I and III, and tissue inhibitor of metalloproteinase 1 (TIMP-1) by cultured fibroblasts by means of RT-PCR and ELISA. Our results showed that synthetic HNP-1 increased the expression of proalpha1(I) collagen mRNA and protein. In contrast, the expression of MMP-1 was decreased at both the mRNA and protein levels. Our observations suggest that HNP-1 may promote wound repair by enhancing extracellular matrix deposition and by controlling its degradation.

火山灰土壌で覆われ,農耕地としての土地利用の割合が高い3つの小流域での浮流土砂の特徴を明らかにした.流域の表層地質の透水性が高いことから,流出率は小さいが,火山灰土壌は軽くまた固結が弱いことや凍結土壌により融雪時期に地表流が発生し,浮流土砂量が多く観測される.浮流土砂量は,既報されている流量(Q)と浮遊土砂量(Qs)の経験式,Qs=(4×10-8～6×10-6)Q2より3～4桁ほどオーダーが高い.また,融雪期では,降雨期より流水中の懸濁物質の濃度が高いことが特徴的である.浮流土砂の粒度分布をみると,農地の土壌と類似し,農地を土砂の生成起源と考えられる.浮流土砂は粒径0.1mm以下の細かいシルトを多く含み,wash loadとして流下するものが多く,河川での沈砂はわずかと考えられる.すなわち,農地から河川へ流入する前に土砂流出抑止対策を行うことが効果的である.

Background: Heavy colonization of atopic dermatitis (AD) with Staphylococcus aureus is well documented. The isolation rate of methicillin-resistant S. aureus is high in strains from AD in Japan. Our objective in the present study was to investigate the actions of farnesol and xylitol against S. aureus for the control of AD skin lesion-colonizing S. aureus.Methods: We examined the actions of farnesol on plasma coagulation and superantigenic exotoxin production by S. aureus, the antimicrobial activity of β-lactam antibiotics combined with farnesol at concentrations below the minimal inhibitory concentration (MIC) and the effect of xylitol on glycocalyx production. Results: Coagulation by S. aureus cells was inhibited in plasma containing farnesol at a concentration of 1/12 of the MIC (100 µg/ml) after incubation for 24 h. The production of superantigenic exotoxins by S. aureus cells with farnesol (100 µg/ml) was about 10 times lower than that by S. aureus cells alone. The MICs of ampicillin and cefdinir against S. aureus were reduced to ≤0.06 µg/ml in Mueller-Hinton agar plates with farnesol (100 µg/ml). We suggest that farnesol at concentrations above the MIC had a suppressive effect against S. aureus cells in the exponential and stationary phase and acted on the cell wall of S. aureus cells in both phases. Conclusions: Farnesol is a promising adjuvant agent against S. aureus skin infections treated with β-lactam antibiotics. Further, 5% xylitol inhibited glycocalyx production by S. aureus cells and consequently had a suppressive effect on the colonization of S. aureus on the horny cells of AD lesions.

In 2003, we started autologous bone marrow cell infusion (ABMi) therapy for treating liver cirrhosis. ABMi therapy uses 400 mL of autologous bone marrow obtained under general anesthesia and infused mononuclear cells from the peripheral vein. The clinical study expanded and we treated liver cirrhosis induced by HCV and HBV infection and alcohol consumption. We found that the ABMi therapy was effective for cirrhosis patients and now we are treating patients with combined HIV and HCV infection and with metabolic syndrome-induced liver cirrhosis. Currently, to substantiate our findings that liver cirrhosis can be successfully treated by the ABMi therapy, we are conducting randomized multicenter clinical studies designated "Advanced medical technology B" for HCV-related liver cirrhosis in Japan. On the basis of our clinical study, we developed a proof-of-concept showing that infusion of bone marrow cells (BMCs) improved liver fibrosis and sequentially activated proliferation of hepatic progenitor cells and hepatocytes, further promoting restoration of liver functions. To treat patients with severe forms of liver cirrhosis, we continued translational research to develop less invasive therapies by using mesenchymal stem cells derived from bone marrow. We obtained a small quantity of BMCs under local anesthesia and expanded them into mesenchymal stem cells that will then be used for treating cirrhosis. In this review, we present our strategy to apply the results of our laboratory research to clinical studies. Copyright © 2014, Mary Ann Liebert, Inc.

血液透析 (HD) 患者の腎性貧血の機序を解明するため, HD導入期から全くrHuEPOの投与を必要としない症例および一時rHuEPOが投与されていたが, 貧血改善後投与中止例で, ともにヘマトクリット値 (Ht) が30%以上に維持されている患者を非投与群 (14例) とし, rHuEPO週3回HD後静注により5か月の観察期間中Htが30%以上に維持されている患者を投与群 (14例) として, 両群の比較検討を行った. その結果, 非投与群の赤血球 (RBC), ヘモグロブリン (Hb), Ht, 総鉄結合能 (TIBC), 不飽和鉄結合能 (UIBC), およびトランスフェリンは投与群に比して有意に高値を, フェリチンは有意に低値を示した. 非投与群では, フェリチンとトランスフェリンの間, フェリチンとHtの間にそれぞれ有意な負の相関を, トランスフェリンとHtの間に有意な正の相関を認めた. トランスフェリンは, HD患者の栄養状態および貧血の評価として重要である.

Defensins are widely distributed and broad-spectrum antimicrobial peptides with activities against bacteria, fungi, and enveloped viruses. Defensins have been isolated from granules of neutrophils from humans, rabbits, rats, and guinea pigs. They have also been found in lung macrophages as well as in Paneth cells of the human, rabbit, and mouse small intestine. The human β-defensin-2 was recently isolated from human skin. In this study, we detected the expression of mRNA for the defensin cryptdin in BALB/c mouse skin by means of reverse transcriptase PCR amplification. Expression was also detected in dispase-separated epidermis and cultured keratinocytes, but expression was not detected in fibroblasts. The expression of cryptdin mRNA was found to begin on embryonic day 17.5. As determined with specific primers, the cDNA sequence cloned from the skin was found to be identical to that previously reported for cryptdin-5. cDNA derived from cultured keratinocytes demonstrated the sequences of the cryptdin-6 and cryptdin-1 isoforms. In situ hybridization analysis showed that the mRNA of cryptdin was expressed in the suprabasal keratinocytes of the skin in embryonic and neonatal days and then shifted to the hair bulbs in the skin of adult mice.

Oculocutaneous albinism type 4 (OCA4) is an autosomal recessive hypopigmentary disorder caused by mutations in the Membrane-Associated Transporter Protein gene (SLC45A2). The SLC45A2 protein is a 530-amino-acid polypeptide that contains 12 putative transmembrane domains, and appears to be a transporter that mediates melanin synthesis. Eighteen pathological mutations have been reported so far. In this study, six novel mutations, p.Y49C (c.146A > G), p.G89R (c.265G > A), p.C229Y (c.686G > A), p.T437A (c.1309A > G), p.T440A (c.1318A > G) and p.G473D (c.1418G > A) were found in eight Japanese patients with various clinical phenotypes. The phenotypes of OCA4 were as various as the other types of OCA and probably depended on the mutation sites in the SLC45A2 gene.

We report a unique case of acute cholecystitis due to strangulation of a floating gallbladder by the lesser omentum, which could be detected by abdominal ultrasonography. We believe this case to be the first case of reported literatures in English.

Prolidase deficiency is an autosomal recessive inherited disease characterized clinically by frequent infections, mental retardation, and various skin lesions. Fundamental treatments for these manifestations have not been established. We performed adenovirus-mediated gene transfer of human prolidase cDNA into fibroblasts from patients with prolidase deficiency. Infection with the adenovirus vector carrying human prolidase cDNA increased prolidase activity in fibroblasts up to approximately 7.5 times of that of normal control fibroblasts. This indicates the feasibility of adenovirus-mediated gene therapy to treat patients with prolidase deficiency in the future.

Insulin resistance (IR) increases during the early stages of hepatitis C virus (HCV)-related chronic liver disease and is a sign of poor prognosis as well as a risk factor for hepatic fibrosis and hepatocellular carcinoma. We aimed to determine the factors affecting IR in HCV-related chronic liver disease.We retrospectively examined 71 patients with HCV-related chronic liver disease and analyzed various parameters, including amino acids, as possible predictors of IR. IR was assessed using the Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR). Amino acids were assayed by examining branched-chain amino acids (BCAA), tyrosine level, and the ratio of BCAA to tyrosine level (BTR).HOMA-IR was significantly correlated with body mass index, platelet count, prothrombin time, hemoglobin, total bilirubin, total protein, albumin, total cholesterol, fasting glucose, BTR (r = -0.46, P = 0.0001) and tyrosine (r = 0.55, P 0.0001). However, BCAA were not significantly correlated with HOMA-IR (r = -0.21, P = 0.082). In multivariate analysis, only two factors were identified as independent parameters contributing to a HOMA-IR of 2.5 or more: total cholesterol (odds ratio [OR], 6.511; 95% confidence interval [95% CI], 1.554-27.284; P = 0.010) and tyrosine (OR, 4.839; 95% CI, 1.087-21.549; P = 0.039).Serum tyrosine levels may be associated with IR in patients with HCV-related chronic liver disease.

Goltz syndrome or Focal dermal hypoplasia (FDH) is an X-linked dominant disorder characterized by malformations affecting the skin, eyes, central nervous system, and skeletonC:\GetARef\Refs\focal dermal hypoplasia (2007-).re. Mutations in the PORCN gene were identified as the molecular basis of FDH. We report two cases, one caused by a current mutation c.129G>A, which leads to a nonsense mutation W43X, and the other one caused by a novel mutation, c.386delT. The female patient with the recurrent mutation presented with typical cutaneous symptoms and skeletal abnormality, but the female patient with the novel mutation manifested only cutaneous symptoms, with hypo-pigmentation along Blaschko's lines, mainly on her right hemibody. In the latter case, DNA was isolated from peripheral blood cells, lesional skin, and non-lesional skin. The percentage of cells carrying the mutation estimated by subcloning and sequencing of the PCR products was 3.1% in peripheral blood cells, 21% in lesional skin, and 16% in non-lesional skin. X-chromosome inactivation assay showed a slightly skewed pattern in lesional skin, but a random pattern in non-lesional skin and blood. RT-PCR analysis from skin samples showed that PORCN mRNA of the mutated allele had a 13bp nucleotide insertion created by an alternative splicing site. This resulted in abnormal PORCN protein with in-frame insertion of eight amino acids, TTHRGTDD, instead of the original four amino acids, AQMI (126-129). We report a typical FDH patient with a recurrent PORCN mutation, which was previously identified in a male Japanese FDH patient, and a second femal, an almost unilateral FDH patient with a postzygotic PORCN mutation.

We investigated rolidase gene expression in human skin by means of Northern blot analysis and in situ hybridization. Northern blot analysis revealed that an mRNA species that was specific for prolidase was present in cultured human skin fibroblasts and keratinocytes. In situ hybridization using non-isotopic riboprobes labeled with digoxigenin and an isotopic riboprobe labeled with [35S]UTP localized prolidase gene expression to fibroblasts and endothelial cells of small vessels in scar tissue. Prolidase mRNA was also prominently expressed in keratinocytes near the basal layer overlying scar tissue. These findings indicate that prolidase may have an important role in wound healing.

62歳の男性。1990年7月に当院循環器内科で突発性拡張型心筋症の診断を受け, 2001年5月10日から塩酸アミオダロン(アンカロン®)を内服している。2002年1月頃から両眼囲に自覚症状のない紅斑が出現し, 徐々に拡大してきたため同年12月27日に当科を受診した。血液検査にてミオグロビン, アルドラーゼの上昇を認め, 皮膚筋炎や光線過敏症を疑った。筋電図, 病理組織学的所見から皮膚筋炎を否定した。光線照射テストでは異常を認めなかった。その後の検査でfree T4低下, TSH上昇, 血中総ヨード値の高値が認められ, 塩酸アミオダロン内服に伴う甲状腺機能低下症と診断した。レボチロキシンナトリウム(チラージンS®)の内服を開始後, 甲状腺機能は改善し, 眼瞼の紅斑も軽快傾向にある。

Background Neutrophilic eccrine hidradenitis (NEH) is an uncommon, self-limited dermatosis usually attributed to anti-cancer chemotherapy. It is characterized histologically by necrosis of the eccrine gland and neutrophilic infiltrate. Observations We saw NEH in a 5-year-old boy with acute lymphoblastic leukemia and a 4-year-old girl with acute monocytic leukemia. NEH developed after the anti-leukemic chemotherapy including high dose cytarabine. The eruption was composed of vesicles, papules, and plaques. Conclusions Histological findings were compatible with those described in the literature. NEH in our two patients could be attributed to high doses of cytarabine.

Summary Background. Cytotoxic T lymphocytes (CTLs) have been recognized as an important effector cell in Behçet disease (BD). Granulysin is a cytolytic granule protein expressed by CTLs and natural killer cells. Aim. To evaluate the involvement of granulysin-producing T cells in the pathogenesis of BD. Methods. Using immunohistochemistry, lymphocyte subsets expressing granulysin were investigated in mucocutaneous lesions of BD. Serum granulysin levels were assayed by ELISA. Results. Granulysin-positive cells were seen in specimens from oral ulcers, genital ulcers and acne-like eruptions, but not erythema nodosum-like lesions. Both CD4+ and CD8+ T cells expressed granulysin. Serum granulysin levels did not correlate with disease activity in BD. Conclusion. Immune reactions mediated by granulysin-positive CTLs may play an important role in the pathogenesis of acne-like eruptions, oral ulcers and genital ulcers in BD.

Prolidase deficiency is an autosomal recessive disorder with highly variable symptoms, including mental retardation, skin lesions, and abnormalities of collagenous tissues. In Japanese female siblings with polypeptide negative prolidase deficiency, and with different degrees of severity of skin lesions, we noted an abnormal mRNA with skipping of 192 bp sequence corresponding to exon 14 in lymphoblastoid cells taken from these patients. Transfection and expression analyses using the mutant prolidase cDNA revealed that a mutant protein translated from the abnormal mRNA had an Mr of 49,000 and was enzymatically inactive. A 774-bp deletion, including exon 14 was noted in the prolidase gene. The deletion had termini within short, direct repeats ranging in size of 7 bp (CCACCCT). The "slipped mispairing" mechanism may predominate in the generation of the deletion at this locus. This mutation caused a 192-bp in-frame deletion of prolidase mRNA and was inherited from the consanguineous parents. The same mutation caused a different degree of clinical phenotype of prolidase deficiency in this family, therefore factor(s) not related to the PEPD gene product also contribute to development of the clinical symptoms. Identification of mutations in the PEPD gene from subjects with prolidase deficiency provides further insight into the physiological role and structure-function relationship of this biologically important enzyme.

Background Brunsting-Perry pemphigoid is a rare subepidermal blistering disease characterized by scarring blisters on the head and neck. However, the identity of the responsible autoantigens is still unresolved. Methods We reported a patient with epidermolysis bullosa acquisita who had clinical features typical of Brunsting-Perry pemphigoid and investigated the involved type VII collagen epitopes. The patient was a 65-year-old Japanese woman with a 20-month history of recurrent subepidermal bullae on her head, face, and neck. Results Immunoblot studies revealed that the serum of this patient reacted with type VII collagen, specifically with the noncollagenous domain 1 and the triple-helical domain. The patient responded completely to colchicine monotherapy. Limitations This study was performed on only one case. Conclusion This study suggests that Brunsting-Perry pemphigoid may be a clinical variant of epidermolysis bullosa acquisita.

Crude enzyme solutions of prolidase were extracted from cultured human skin fibroblasts derived from control and prolidase-deficient sisters. Two forms of prolidases (prolidase-I and II) were partially purified by high performance liquid chromatography equipped with an ion exchange column. On gel filtration, the relative molecular weights of prolidase-I and II were estimated to be MW = 105,000 and 151,000, respectively. The substrate specificity of partially purified prolidase-I and II in control fibroblasts was estimated against Gly-Pro, Ala-Pro, Met-Pro. Each form of prolidase differed in its substrate specificity. In prolidase-deficient sisters, the elder with typical clinical manifestations and the younger with only slight clinical manifestations, the activity of prolidase-I was absent. However, the activity of prolidase-II was sufficiently present in both sisters. The substrate specificity of prolidase-II in the patients was similar to that of control. No difference in substrate specificity was found between these two patients.