[Marked improvement in renal tubular markers after switching from adefovir to tenofovir alafenamide in a case of Fanconi syndrome diagnosed through high ALP levels].

A woman in her 60s visited our hospital due to elevation of ALP (1357U/L). The patient had been treated with lamivudine (LAM) in 2005, LAM+adefovir (ADV) in 2009, and ADV+entecavir in 2015 for chronic hepatitis B (CH-B). The ALP isozyme was predominantly bone type. Urinary ß-2 microglobulin (MG) and α-1MG increased to 49635µg/L and 64.1mg/L, respectively. Though no fractures were found during bone scintigraphy, the patient was diagnosed with Fanconi syndrome. However, 3 months after switching from ADV to tenofovir alafenamide (TAF), ALP decreased to 856U/L, and urinary ß-2MG and α-1MG decreased to 624µg/L and 6.0mg/L, respectively. Fanconi syndrome should be considered when an increase in ALP is observed in patients treated with ADV, and urinary ß-2MG and α-1MG assays are useful for establishing a diagnosis. Switching from ADV to TAF was an effective therapeutic option.

Sarcoid Myositis with Anti-Ku Antibody Consistent with both Sarcoidosis and Polymyositis.

We herein describe a case of sarcoid myositis with anti-Ku antibody positivity. Pathological findings of the muscle were compatible with sarcoidosis, but could not be completely distinguished from myositis diseases that arise from other causes. According to a physical examination, pathological findings, the detection of anti-Ku antibody and the human leukocyte antigen (HLA)-DPB1 allele, we strongly suspected that the patient developed both sarcoidosis and polymyositis. Sarcoidosis is often complicated by autoimmune diseases. This case suggests the possibility that sarcoidosis and other autoimmune diseases may have common causal genetic factors.

An autopsy study of combined pulmonary fibrosis and emphysema: correlations among clinical, radiological, and pathological features.

BACKGROUND: Clinical evaluation to differentiate the characteristic features of pulmonary fibrosis and emphysema is often difficult in patients with combined pulmonary fibrosis and emphysema (CPFE), but diagnosis of pulmonary fibrosis is important for evaluating treatment options and the risk of acute exacerbation of interstitial pneumonia of such patients. As far as we know, it is the first report describing a correlation among clinical, radiological, and whole-lung pathological features in an autopsy cases of CPFE patients. METHODS: Experts retrospectively reviewed the clinical charts and examined chest computed tomography (CT) images and pathological findings of an autopsy series of 22 CPFE patients, and compared these with findings from 8 idiopathic pulmonary fibrosis (IPF) patients and 17 emphysema-alone patients. RESULTS: All patients had a history of heavy smoking. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC%) was significantly lower in the emphysema-alone group than the CPFE and IPF-alone groups. The percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) was significantly lower in the CPFE group than the IPF- and emphysema-alone groups. Usual interstitial pneumonia (UIP) pattern was observed radiologically in 15 (68.2%) CPFE and 8 (100%) IPF-alone patients and was pathologically observed in all patients from both groups. Pathologically thick-cystic lesions involving one or more acini with dense wall fibrosis and occasional fibroblastic foci surrounded by honeycombing and normal alveoli were confirmed by post-mortem observation as thick-walled cystic lesions (TWCLs). Emphysematous destruction and enlargement of membranous and respiratory bronchioles with fibrosis were observed in the TWCLs. The cystic lesions were always larger than the cysts of honeycombing. The prevalence of both radiological and pathological TWCLs was 72.7% among CPFE patients, but no such lesions were observed in patients with IPF or emphysema alone (p=0.001). The extent of emphysema in CPFE patients with TWCLs was greater than that in patients without such lesions. Honeycombing with emphysema was also observed in 11 CPFE patients. CONCLUSIONS: TWCLs were only observed in the CPFE patients. They were classified as lesions with coexistent fibrosing interstitial pneumonia and emphysema, and should be considered an important pathological and radiological feature of CPFE.

Mixed-type multicentric Castleman's disease developing during a 17-year follow-up of sarcoidosis.

Multicentric Castleman's Disease (MCD) is a systemic disease characterized by generalized lymphadenopathy and the proliferation of plasma cells. The development of MCD in a patient with preexisting sarcoidosis has not been previously reported. We herein describe a case of MCD developing in a 78-year-old woman with a 17-year history of sarcoidosis. The patient's serum interleukin-6 (IL-6) levels were only slightly elevated; however, the IL-6 levels in the fluid of both pleural effusion and ascites were markedly elevated. The administration of steroid-pulse therapy and prednisolone was ineffective in treating the MCD, although treatment with tocilizumab proved highly effective.

Upper gastrointestinal sarcoidosis: report of three cases.

Involvement of the upper gastrointestinal tract in sarcoidosis is rare, and an optimal treatment regimen remains to be determined. Here, we report 3 cases of upper gastrointestinal sarcoidosis in Japanese patients aged 57-70 years with or without epigastric symptoms and describe the clinical features, laboratory data, and upper endoscopy and pathological findings. Upper gastrointestinal sarcoidosis was diagnosed based on the presence of noncaseating epithelioid cell granuloma in the lamina propria in the stomach or duodenum. In conclusion, the possibility of upper gastrointestinal sarcoidosis should be considered in patients with epigastric symptoms and a history of sarcoidosis, even in those with stable disease.

Primary bypass surgery from the descending aorta to the iliac arteries for a severely calcified aorta: report of two cases.

We herein report two patients with end-stage renal failure who complained of disabling claudication due to abdominal aortic atherosclerosis. Both were on chronic hemodialysis for more than 15 years, and their abdominal aorta was densely calcified. We elected to perform a descending aorta to iliac artery bypass in order to avoid hazardous clamping of the calcified aorta. Hemodialysis was able to be resumed on the first postoperative day. They tolerated the operation well and their symptoms disappeared. This operative procedure is therefore considered to be a useful option for patients with a porcelain aorta who are on chronic hemodialysis.

Conduction performance of collateral vessels induced by vascular endothelial growth factor or basic fibroblast growth factor.

OBJECTIVE: In the present study, we delivered vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) gene to a rabbit model of hind limb ischemia utilizing an ex vivo method of gene transfer, and evaluated the functional performance of the developed collateral vessels. METHOD: The left femoral artery of a male Japanese White rabbit was excised to induce limb ischemia, and a section of skin was resected for culture of auto-fibroblasts. Twenty days later, the VEGF gene, bFGF gene or beta-galactosidase gene (LacZ) was adenovirally transferred to the cultured auto-fibroblasts (5x10(6) cells), and the next day, a pair of specifically infected fibroblasts (total 1x10(7) cells) was injected via the left internal iliac artery of the same rabbit. Pairs of transferred genes into the fibroblasts were as follows: LacZ/LacZ (control group), VEGF/LacZ (VEGF group), bFGF/LacZ (FGF group) and VEGF/bFGF (combination group). Twenty-eight days after cell administration, collateral development and its function were evaluated. RESULTS: Calf blood pressure ratio, resting blood flow of the left iliac artery and capillary density of ischemic muscle showed similar degrees of angiogenic effects in the VEGF and FGF groups, which were significantly greater than those in the control group. On the contrary, angiographic score, collateral conductance and smooth muscle cell (SMC)-positive vessel density in the FGF group were significantly greater than those in the VEGF group. In the combination group, collateral conductance showed synergistic effects, and in vivo blood flow and smooth muscle cell-positive vessel density revealed additive effects of VEGF and bFGF. CONCLUSION: These findings suggested that bFGF-induced collateral development exceeded VEGF-induced collateral development in the induction of arteriogenesis, and that combined gene delivery of VEGF and bFGF produced additive or synergistic effects of collateral development as compared with the effects induced by transfer of each gene alone.

Suppression of macho-1-directed muscle fate by FGF and BMP is required for formation of posterior endoderm in ascidian embryos.

Specification of germ layers is a crucial event in early embryogenesis. In embryos of the ascidian, Halocynthia roretzi, endoderm cells originate from two distinct lineages in the vegetal hemisphere. Cell dissociation experiments suggest that cell interactions are required for posterior endoderm formation, which has hitherto been thought to be solely regulated by localized egg cytoplasmic factors. Without cell interaction, every descendant of posterior-vegetal blastomeres, including endoderm precursors, assumed muscle fate. Cell interactions are required for suppression of muscle fate and thereby promote endoderm differentiation in the posterior endoderm precursors. The cell interactions take place at the 16- to 32-cell stage. Inhibition of cell signaling by FGF receptor and MEK inhibitor also supported the requirement of cell interactions. Consistently, FGF was a potent signaling molecule, whose signaling is transduced by MEK-MAPK. By contrast, such cell interactions are not required for formation of the anterior endoderm. Our results suggest that another redundant signaling molecule is also involved in the posterior endoderm formation, which is likely to be mediated by BMP. Suppression of the function of macho-1, a muscle determinant in ascidian eggs, by antisense oligonucleotide was enough to allow autonomous endoderm specification. Therefore, the cell interactions induce endoderm formation by suppressing the function of macho-1, which is to promote muscle fate. These findings suggest the presence of novel mechanisms that suppress functions of inappropriately distributed maternal determinants via cell interactions after embryogenesis starts. Such cell interactions would restrict the regions where maternal determinants work, and play a key role in marking precise boundaries between precursor cells of different tissue types.