Primary AA type amyloidosis of the urinary bladder: a case report

Primary amyloidosis of the urinary bladder is a rare disease entity. A total of 61 cases have been reported in the Japanese literature, and most of them were AL type amyloidosis. We report here a case of primary AA type amyloidosis. A 52-year-old man presented with a chief complaint of asymptomatic gross hematuria. Cystoscopy revealed yellowish elevated lesions, transurethral mucosal biopsies were performed, and the histopathological diagnosis indicated a primary AA type amyloidosis of the urinary bladder. Systemic amyloidosis was clinically eliminated. The yellowish lesions in the bladder through cystoscopy disappeared spontaneously one year later without any specific treatment, but periodical work-up may be necessary to rule out recurrence of the disease or bladder tumor.     

Trastuzumab-mediated antibody-dependent cellular cytotoxicity against esophageal squamous cell carcinoma.

PURPOSE: In the present study, we investigated the degree of protein expression and gene amplification of HER-2 in esophageal squamous cell carcinoma (SCC) cell lines and freshly isolated tumors, and trastuzumab-mediated biological activity, in particular antibody-dependent cellular cytotoxicity (ADCC) against HER-2-expressing esophageal SCC cell lines. EXPERIMENTAL DESIGN: Ten different SCC cell lines with various levels of HER-2 status evaluated by flow cytometry, immunocytochemistry (HercepTest), and fluorescence in situ hybridization were evaluated for ADCC, growth inhibitory, or apoptosis-inducing activities mediated by trastuzumab. RESULTS: Trastuzumab induced ADCC against HER-2-expressing esophageal SCC and the activities reflected the degree of HER-2 expression analyzed by flow cytometric analysis, but not by HercepTest nor fluorescence in situ hybridization analysis. Furthermore, trastuzumab-mediated ADCC against transforming growth factor-beta-producing SCC was enhanced by the treatment with SB-431542, which is a selective inhibitor of the phosphorylation induced by transforming growth factor-beta. There were very marginal effects of anti-proliferative or apoptosis-inducing activities mediated by trastuzumab for HER-2-expressing esophageal SCC. CONCLUSION: HER-2-expressing esophageal SCC cells could be killed by trastuzumab-mediated ADCC and the activity reflected the degree of HER-2 expression detected by flow cytometry.     

A Highly Specific and Sensitive Radioimmunoassay of Caerulein,An Analogue of Cholecystokinin-8

Abstract

A highly specific and sensitive competitive radioimmunoassay was developed for caerulein (CLN), an analogue of cholecystokinin-8 (CCK-8), in plasma and brain. Antiserum was produced in rabbit by immunization with Nδ-[CLN-(1-6)]-ornithine amide conjugated with bovine serum albumin by the glutaraldehyde method. Nα-[CLN-(1-6)]-lysine amide was labelled with ¹²⁵I-Bolton & Hunter reagent and used as a labelled antigen after purification by high-performance liquid chromerography. This assay was highly specific for CLN, and cross reactivities for other related peptides, CCK-4, CCK-8, gastrin-I, and gastrin-(14–17), were not observed (<0.01%). The limits of determination in biological specimens after CLN administration were 11 pg/ml in human plasma and rat plasma and 80 pg/g in rat brain. This study showed that the slight structure difference between hapten and ¹²⁵I-labelled antigen is important to the assay performance.     

Whole‐exome sequencing and host cell reactivation assay lead to a diagnosis of xeroderma pigmentosum group D with mild ultraviolet radiation sensitivity

A case of xeroderma pigmentosum (XP) group D in a 39‐year‐old Japanese man is reported. The patient had suffered from moderate to severe solar sensitivity and freckle‐like pigmented macules in sun‐exposed areas since 6 years of age, and developed skin malignancies such as squamous cell carcinoma, actinic keratosis, Bowen’s disease and basal cell carcinoma. The minimal erythema dose for ultraviolet (UV) radiation was decreased with a delayed peak reaction. The level of unscheduled DNA synthesis of fibroblasts from the patient was 70% of normal, while they expressed POLH, a gene product responsible for the XP variant. Whole‐exome sequencing indicated that the patient harbored a homozygous mutation of c.1802G>T, p.Arg601Leu in ERCC2. A genetic complementation test was carried out by host cell reactivation assay, which showed that the patient’s fibroblasts recovered only when they were transfected with XPD cDNA, confirming the diagnosis of XP‐D. Arg601Leu mutation in ERCC2 may be related to mild UV radiation sensitivity and moderate skin lesions.     

Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: A randomized controlled trial

Bile acid sequestrants (BAS) lower plasma low density lipoprotein levels and improve glycemic control. Colestimide, a BAS, has been claimed by computed tomography to reduce liver fat. Therefore, we examined the efficacy of colesevelam, a potent BAS, to decrease liver fat in patients with biopsy-proven nonalcoholic steatohepatitis (NASH). Liver fat was measured by a novel magnetic resonance imaging (MRI) technique, the proton-density-fat-fraction (PDFF), as well as by conventional MR spectroscopy (MRS). Fifty patients with biopsy-proven NASH were randomly assigned to either colesevelam 3.75 g/day orally or placebo for 24 weeks. The primary outcome was change in liver fat as measured by MRI-PDFF in colocalized regions of interest within each of the nine liver segments. Compared with placebo, colesevelam increased liver fat by MRI-PDFF in all nine segments of the liver with a mean difference of 5.6% (P = 0.002). We cross-validated the MRI-PDFF-determined fat content with that assessed by colocalized MRS; the latter showed a mean difference of 4.9% (P = 0.014) in liver fat between the colesevelam and the placebo arms. MRI-PDFF correlated strongly with MRS-determined hepatic fat content (r(2) = 0.96, P < 0.0001). Liver biopsy assessment of steatosis, cellular injury, and lobular inflammation did not detect any effect of treatment. Conclusion: Colesevelam increases liver fat in patients with NASH as assessed by MRI as well as MRS without significant changes seen on histology. Thus, MRI and MRS may be better than histology to detect longitudinal changes in hepatic fat in NASH. Underlying mechanisms and whether the small MR-detected increase in liver fat has clinical consequences is not known. (HEPATOLOGY 2012;56:922-932).     

Changes in wall shear stress magnitude after aneurysm rupture

Computational fluid dynamics (CFD) studies on cerebral aneurysms have attempted to identify surrogate hemodynamic parameters to predict rupture risk. We present a case of bilateral mirror image aneurysms, one of which ruptured soon after imaging. Wall shear stress values of the ruptured aneurysm changed by 20–30 % after rupture because of change in the aneurysm shape. Findings from our case suggest that CFD studies comparing unruptured and ruptured aneurysms may not yield valid estimation on aneurysm rupture risk because of changes in aneurysm shape after rupture. Changes in aneurysm shape after rupture should be considered in CFD research.