Caroli's disease associated with hepatolithiasis: a case report and review of the Japanese literature

A 27-year-old woman was admitted to Nagasaki University Hospital complaining of abdominal pain and fever. Percutaneous transhepatic cholangiography showed multiple cystic dilatations of the intrahepatic bile ducts without stone formation. The illness was diagnosed as a pure type of Caroli's disease. No surgical intervention was made. Subsequently, the patient suffered repeated attacks of cholangitis, and six years later, computed tomography demonstrated cystic lesions of both lobes of the liver and stones within the cystic lesions of the right lobe. We collected 62 cases of Caroli's disease reported in the Japanese literature, including our own case. Among them, cholangitis was found in 43.5%, hepatolithiasis in 30.6%, esophageal varices in 17.7% and cholangiocarcinoma in 8.1%. It is difficult to successfully treat Caroli's disease involving both lobes of the liver. Long-term repeated cholangitis could lead to fibrosis of the liver, hepatolithiasis, portal hypertension and cholangiocarcinoma. Considering the above-mentioned aspects of the disease, careful follow-up studies are required in each case.     

Enhanced production of nitric oxide,reactive oxygen species,and pro-inflammatory cytokines in very long chain saturated fatty acid-accumulated macrophages

Background  

Deterioration of peroxisomal β-oxidation activity causes an accumulation of very long chain saturated fatty acids (VLCSFA) in various organs. We have recently reported that the levels of VLCSFA in the plasma and/or membranes of blood cells were significantly higher in patients with metabolic syndrome and in patients with coronary artery disease than the controls. The aim of the present study is to investigate the effect of VLCSFA accumulation on inflammatory and oxidative responses in VLCSFA-accumulated macrophages derived from X-linked adrenoleukodystrophy (X-ALD) protein (ALDP)-deficient mice.     

Prognosis of Parkinson's disease: time to stage III, IV, V, and to motor fluctuations.

We report a long-term outcome on a large cohort of Japanese patients with Parkinson's disease (PD). A total of 1,768 (793 men, 975 women) consecutive patients visited our clinic from 1 January 1989 to 31 December 2002. Among them, 1,183 patients (531 men, 652 women) came to our clinic within 5 years from the onset of disease and at the Hoehn & Yahr Stage III or less at the first visit. Long-term outcome was evaluated in this subcohort of the patients. We examined the duration to reach Stage III, IV, and V, and the duration to develop wearing off and dyskinesia. Time to reach Stage III was slightly but significantly shorter in women, in that 23.8% of men and 35.3% of women reached Stage III by the end of the 5th year; 49.7% of men and 63.3% of women reached Stage III by the end of the 10th year, and 88.9% of men and 79.9% of women by the end of the 15th year (P < 0.001). Also, durations to develop wearing off and dyskinesia were shorter in women compared to men. These data suggest that the disease progression may be slightly faster for women. Young-onset patients showed significantly longer duration to reach Stage III, IV, and V but shorter duration to develop wearing off and dyskinesia. Not many studies are available in the literature on the long-term outcome of PD, and our data would be useful as a reference.     

Impact of Intraoperative 3-Tesla MRI on Endonasal Endoscopic Pituitary Adenoma Resection and a Proposed New Scoring System for Predicting the Utility of Intraoperative MRI

The aim of this study was to evaluate the impact of 3-Tesla intraoperative high-field magnetic resonance imaging (3T-iMRI) for pituitary adenoma resection, and to propose a new scoring system for predicting the utility of 3T-iMRI. This retrospective study evaluated 82 patients with pituitary adenoma who underwent purely endoscopic endonasal resection with 3T-iMRI between 2015 and 2019. 3T-iMRI revealed unexpected residual tumor in 39 cases (47.6%), which led to further resection and contributed to upgrading of the resection level in 28 cases (34.1%), which led to gross total resection rates (GTRs) of 67.1% and near total resection of 15.9%. To construct a new scoring system, patients were divided into a discovery cohort (56 patients) and a validation cohort (26 patients). Three variables for the scoring system were selected according to a univariate analysis of the discovery cohort: the size of the tumor (>20 mm: 1 point), the presence of suprasellar tumor lobulation (1 point) and the history of previous operations (1 point). The risk of additional resection after iMRI was well stratified by this scoring system (range 0–3; p = 0.0037 for trend). Robustness of the system was confirmed in the validation cohort (0 points, 0%; 1 point, 30.8%; 2 points, 70.0%; 3 points, 100%; p = 0.0116 for trend). These results indicate that 3T-iMRI optimized the extent of resection, even with the use of an endoscope, and that the proposed scoring system is useful for predicting whether 3T-iMRI is likely to be of value for a particular patient.     

Inhibition of protein kinase CK2 prevents the progression of glomerulonephritis

Glomerulonephritis (GN) is a progressive inflammation that may be caused by a variety of underlying disorders. It is the primary cause of chronic renal failure and end-stage renal disease, which require dialysis and transplantation worldwide. Immunosuppressive therapy has been used to treat GN clinically, but this treatment has had insufficient therapeutic effects. Here, we show that protein kinase CK2 is a key molecule in the progression of GN. cDNA microarray analysis identified CK2alpha, the catalytic subunit of CK2, as a GN-related, differentially expressed gene. Overexpression of CK2alpha was noted in the proliferative glomerular lesions in rat GN models and in renal biopsy specimens from lupus nephritis or IgA nephropathy patients. Administration of either antisense oligodeoxynucleotide against CK2alpha or low molecular weight CK2-specific inhibitors effectively prevented the progression of renal pathology in the rat GN models. The resolution of GN by CK2 inhibition may result from its suppression of extracellular signal-regulated kinase-mediated cell proliferation, and its suppression of inflammatory and fibrotic processes that are enhanced in GN. Our results show that CK2 plays a critical role in the progression of immunogenic renal injury, and therefore, CK2 is a potential target for GN therapy.     

Infusion of angiotensin II reduces loss of glomerular capillary area in the early phase of anti-Thy-1.1 nephritis possibly via regulating angiogenesis-associated factors

BACKGROUND: Although angiotensin II (Ang II) is involved in the progression of renal diseases, infusion of Ang II was reported to surprisingly ameliorate the early phase of anti-Thy-1.1 nephritis. Considering the known proangiogenic effect of Ang II and that angiogenic glomerular capillary repair is required for the recovery of damaged glomeruli in rat anti-Thy-1.1 nephritis, we hypothesized that Ang II infusion starting prior to the initiation of nephritis may induce the expression of angiogenic growth factors such as vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1), resulting in the increased glomerular capillary area in the early phase. METHODS: Ang II was infused (170 ng/min) in rats, and 5 days later, nephritis was induced by the administration of monoclonal 1-22-3 antibodies. Ang II type 1 or type 2 receptor antagonist (AT(1)R or AT(2)R, respectively) (losartan or PD123319, respectively) was coadministered. RESULTS: Ang II infusion affected on neither the deposition of Ig nor mesangiolysis in the initial phase, and resulted in the aggravation of creatinine clearance at day 14 and 35 after initiating anti-Thy-1.1 nephritis. Histologic alterations were ameliorated accompanied by reduced loss in rat endothelial cell antigen (RECA)-1(+) endothelial area in Ang II-infused nephritic rats on day 6 and 14 as compared to control nephritic group, and nephritic alterations were mostly resolved on day 35 in both groups. At the early stage (day 6), glomerular expression of VEGF and receptors flk-1 and flt-1 as well as Ang-1, and receptor Tie2 were increased, and glomerular monocyte infiltration and the expression of angiopoietin-2 (Ang-2), a natural antagonist of Ang-1, were reduced. Both Ang II receptors were involved in the regulation of angiogenic factors and receptors. CONCLUSION: These results demonstrate that infusion of exogenous Ang II starting prior to the induction of nephritis activates VEGF and Ang-1 signaling regulated via both Ang II receptors, potentially leading to the accelerated recovery of injured glomerular endothelial cells in the early phase of anti-Thy-1.1 nephritis. Increased expression of VEGF and Ang-1 on podocytes further suggests the crucial association of endothelial cells and podocytes in maintaining proper glomerular capillary structures.