The diagnosis of metastatic clear cell renal cell carcinoma (CC-RCC) can be difficult because of its morphologic heterogeneity and the increasing use of small image-guided biopsies that yield scant diagnostic material. This is further complicated by the degree of morphologic and immunophenotypic overlap with non-renal neoplasms and tissues, such as adrenal cortex. In this study, a detailed immunoprofile of 63 adrenal cortical lesions, which included 54 cortical neoplasms, was compared with 185 metastatic CC-RCC using traditional [anti-calretinin, CD10, anti-chromogranin, anti-EMA, anti-inhibin, anti-melanA, anti-cytokeratins (AE1/AE3 and AE1/CAM5.2), anti-renal cell carcinoma marker (RCCma), and anti-synaptophysin)] and novel [anti-carbonic anhydrase-IX (CAIX), anti-hepatocyte nuclear factor-1b (HNF-1b), anti-human kidney injury molecule-1 (hKIM-1), anti-PAX-2, anti-PAX-8, anti-steroidogenic factor-1 (SF-1), and anti-T cell immunoglobulin mucin-1 (TIM-1)] antibodies. Tissue microarray methodology was used to simulate small image-guided biopsies. Staining extent and intensity were scored semiquantitatively for each antibody. In comparing different intensity thresholds required for a ‘‘positive’’ result, ≥2+ was identified as optimal for diagnostic sensitivity/specificity. For the distinction of adrenal cortical lesions from metastatic CC-RCC, immunoreactivity for the adrenal cortical antigens SF-1 (86% adrenal; 0% CC-RCC), calretinin (89% adrenal; 10% CC-RCC), inhibin (86% adrenal; 9% CC-RCC), and melanA (86% adrenal; 10% CC-RCC) and the renal epithelial antigens hKIM-1 (0% adrenal; 83% CC-RCC), PAX-8 (0% adrenal; 83% CC-RCC), HNF-1b (0% adrenal; 76% CC-RCC), EMA (0% adrenal; 78% CC-RCC), and CAIX (3% adrenal; 87% CC-RCC) had the most potential utility. The use of the novel renal epithelial markers hKIM-1 (clone AKG7) and/or PAX-8, and the adrenocortical marker SF-1 in an immunohistochemical panel for distinguishing adrenal cortical lesions from metastatic CC-RCC offers improved diagnostic sensitivity and specificity.

Cyclization reaction of a photochromic diarylethene derivative, 1,2-bis(2-methyl-3-benzothienyl)perfluorocyclopentene (BT), in nonpolar alkane solutions with different viscosity was investigated by means of femtosecond−microsecond transient absorption spectroscopy and a time-correlated single-photon counting method. Transient absorption measurements revealed that a ring closure rapidly occurred with a time constant of 450 fs. In addition to this rapid cyclization, transient species with longer lifetimes (ca. 150 ps and ca. 1 μs) were observed. The faster time constant of 150 ps was independent of the solvent viscosity and was assigned to the fluorescence lifetime of a conformer with molecular geometry unfavorable for the ring closure. The longer component was strongly quenched in the solution purged with O2 and was attributed to the triplet state of the open-ring form. Steady-state measurement and nanosecond transient absorption spectroscopy revealed that the cyclization process did not occur via the triplet state of BT. These results indicate that only the rapid reaction taking place in subpicosecond time region was responsible for the cyclization process. The key factors regulating the cyclization reaction of diarylethene derivatives were discussed on the basis of the solvent viscosity dependence, by comparing the present results with those obtained for other diarylethene derivatives.

BACKGROUND: Distinguishing hepatocellular carcinoma (HCC) from adenocarcinoma in fine-needle aspiration biopsies (FNAB) is often diagnostically challenging. Arginase-1 was recently described as a marker of hepatic differentiation in surgical resection specimens. We compared the expression of arginase-1, HepPar-1, and glypican-3 in FNAB of HCC and adenocarcinoma involving the liver. METHODS: Ninety-eight FNABs including 37 primary or metastatic HCCs (30 well or moderately differentiated and 7 poorly differentiated) and 61 adenocarcinomas involving the liver were evaluated for immunohistochemical expression of arginase-1, HepPar-1, and glypican-3 using formalin-fixed paraffin-embedded cell block material. RESULTS: Arginase-1 was more sensitive (81%) than HepPar-1 (70%) or glypican-3 (54%) for HCC. Arginase-1 more often demonstrated diffuse staining, defined as reactivity in >50% of the tumor, in HCC (21 of 37; 57%) compared with HepPar-1 (15 of 37; 41%) and glypican-3 (12 of 37; 32%). Of the 7 poorly differentiated HCCs, 3 (43%) were immunoreactive for both arginase-1 and glypican-3, whereas only 1 (14%) demonstrated HepPar-1 staining. Arginase-1 expression was identified in adenocarcinomas of pancreatic, colorectal, and breast origin, and reactivity was diffuse in 2 pancreatic adenocarcinomas (2 of 15; 13%). CONCLUSIONS: Arginase-1 is a more sensitive marker of hepatic differentiation than either HepPar-1 or glypican-3 in FNAB. In addition, arginase-1 exhibits more diffuse staining in HCC than either HepPar-1 or glypican-3, making interpretation easier in limited FNAB samples. Arginase-1 is not entirely specific for hepatic differentiation, as immunoreactivity can be identified in adenocarcinomas, particularly of pancreatic origin. Cancer (Cancer Cytopathol) 2012;120:230-7.

Solvent polarity dependence of photochromic reactions such as cyclization and cycloreversion of a photochromic diarylethene derivative, 1,2-bis­(2-methyl-3-benzothienyl)­perfluorocyclopentene, was investigated by steady-state spectroscopic and femtosecond laser photolysis methods. For the cyclization reaction, it was revealed that the quantum yield decreased with an increase in solvent polarities, mainly due to the decrease in the fraction of the conformer with C 2 symmetry favorable for the cyclization. This result indicated that the branching ratio for the cyclization and the deactivation to the open-ring isomer at the conical intersection was almost independent of the solvent polarity. On the other hand, it was found for the cycloreversion process that the closed-ring isomer in the S1 state rapidly deactivated into the ground state in competition with the activated process leading to the conical intersection providing a pathway toward both open- and closed-ring minima in the ground state. The cycloreversion reaction quantum yield also decreasing with an increase in the solvent polarity was attributed to larger increase of the direct deactivation into the ground state from the excited state minimum of the closed-ring isomer.

TORU AIZAWA, MD 4OBJECTIVE -The goal of this study was to know the fate of albuminuria in Japanese patients with type 2 diabetes under tight blood pressure and glycemic control.RESEARCH DESIGN AND METHODS -Patients having normoalbuminuria (urinary albumin excretion Ͻ30 mg/g creatinine, n ϭ 179) or microalbuminuria (albumin excretion 30 -299 mg/g creatinine, n ϭ 94) at baseline have been followed up for 8 years: ratio of men to women was 160/113, the mean age was 58 years, pretreatment HbA 1c (A1C) was 8.8%, and blood pressure was 136/76 mmHg. A1C Ͻ6.5% and blood pressure Ͻ130/80 mmHg were targeted, and the A1C of 6.5 Ϯ 0.7% (mean Ϯ SD) and blood pressure of 127 Ϯ 11/72 Ϯ 6 mmHg have been maintained during the 8 years. Development of microalbuminuria or macroalbuminuria (albumin excretion Ն300 mg/g creatinine) in initially normoalbuminuric patients and progression to macroalbuminuria or regression to normoalbuminuria in initially microalbuminuric patients were assessed at year 8.RESULTS -Development occurred in 27 (15%) of the normoalbuminuric patients and progression and regression in 16 (17%) and 20 (21%), respectively, of the microalbuminuric patients. Significant independent relationships existed between development and higher achieved mean systolic blood pressure (SBP) and regression and lower achieved mean SBP. In the patients with achieved mean SBP Ͻ120 mmHg, development was 3%, progression was 11%, and regression was 44% during 8 years. Prediction for nephropathy by blood pressure and glycemia alone was limited. Nevertheless, albumin excretion at year 8 was positively correlated with achieved mean SBP and baseline albuminuria.CONCLUSIONS -Development and progression were low and regression was high with SBP of 120 mmHg, provided A1C was maintained at 6.5%. Diabetes Care 28:2733-2738, 2005D iabetic nephropathy is now the leading cause of end-stage renal failure in Europe, the U.S., and Japan (1), and the establishment of an effective treatment strategy for diabetic nephropathy is of paramount importance. In particular, early intervention is hoped to bring about 1) the prevention of new development of nephropathy, 2) the prevention of progression of early-phase nephropathy, and 3) the regression of existing nephropathy (1-3). Urinary albumin excretion (UAE) is a marker of earlyphase diabetic nephropathy (1-3), and the amount of UAE correlates with renal pathologic changes in both type 1 and type 2 diabetes (4). Accordingly, many studies have been performed with UAE as a marker of diabetic nephropathy (5-7). The development and progression of nephropathy were improved by glycemic and blood pressure controls as expected (5-8). Antihypertensive therapy and improved glycemic control were independent predictors of the regression from micro-to normoalbuminuria (8). In this study, we analyzed the fate of early-phase diabetic nephropathy as indexed by the change in UAE in Japanese patients with type 2 diabetes over an 8-year period. In particular, the relationship between blood pressure and the state of albuminuria...

This study characterized a new unshielded diode detector, the microSilicon (model 60023), for small-field photon beam dosimetry by evaluating the photon beams generated by a TrueBeam STx and a CyberKnife. Temperature dependence was evaluated by irradiating photons and increasing the water temperature from 11.5 to 31.3°C. For Diode E, microSilicon, microDiamond and EDGE detectors, dose linearity, dose rate dependence, energy dependence, percent-depth-dose (PDD), beam profiles and detector output factor (OFdet) were evaluated. The OFdet of the microSilicon detector was compared to the field output factors of the other detectors. The microSilicon exhibited small temperature dependence within 0.4%, although the Diode E showed a linear variation with a ratio of 0.26%/°C. The Diode E and EDGE detectors showed positive correlations between the detector reading and dose rate, whereas the microSilicon showed a stable response within 0.11%. The Diode E and microSilicon demonstrated negative correlations with the beam energy. The OFdet of microSilicon was the smallest among all the detectors. The maximum differences between the OFdet of microSilicon and the field output factors of microDiamond were 2.3 and 1.6% for 5 × 5 mm2 TrueBeam and 5 mm φ CyberKnife beams, respectively. The PDD data exhibited small variations in the dose fall-off region. The microSilicon and microDiamond detectors yielded similar penumbra widths, whereas the other detectors showed steeper penumbra profiles. The microSilicon demonstrated favorable characteristics including small temperature and dose rate dependence as well as the small spatial resolution and output factors suitable for small field dosimetry.

Although cutaneous ovarian metastasis is a rare phenomenon, the prognosis is extremely poor. PAX8 expression is a useful marker that effectively discriminated metastatic ovarian carcinomas from metastatic breast carcinomas and primary adnexal tumors.

Aims  Risk assessment of developing cardiac involvement in systemic sarcoidosis can be challenging because of limited data. Recently, attention has been given to left ventricular and right ventricular (LV and RV) involvement in cardiac sarcoidosis (CS) and its prevalence, relevance, and prognostic value. The aim of this study was to assess the role of biventricular strain to predict prognosis in confirmed sarcoidosis patients. Methods and results  LV and RV longitudinal strains (LSs) were evaluated by 2D speckle tracking in 139 consecutive confirmed sarcoidosis patients without other pre-existing structural heart diseases, and 52 age- and gender-matched control subjects. The primary endpoint was CS-related events (cardiac death or development of cardiac involvement). Sarcoidosis without cardiac involvement had significantly lower LV and RV free wall LS compared with control subjects. Basal LS had a higher area under the curve for differentiation of sarcoidosis in patients without cardiac involvement compared to control (cut-off value: −18% with 89% sensitivity and 69% specificity). During a median period of 50 months, the occurrence of CS-related events was observed in 20 patients. In a multivariate analysis, basal LV LS and RV free wall LS were associated with the events [hazard ratio (HR) 0.72, P < 0.001 and HR: 0.83, P = 0.006, respectively]. Patients with impaired biventricular function had significantly shorter event-free survival than those with preserved biventricular function (P < 0.001). Conclusion  Deterioration of biventricular strain was associated with CS-related events. This information might be useful for clinical evaluation and follow-up in sarcoidosis.