The B-Mode Image-Guided Ultrasound Attenuation Parameter Accurately Detects Hepatic Steatosis in Chronic Liver Disease

The purpose of our study was to evaluate the diagnostic accuracy of the ultrasound-guided attenuation parameter (UGAP) for the detection of hepatic steatosis in comparison with the controlled attenuation parameter (CAP), using histopathology as the reference standard. We prospectively analyzed 163 consecutive chronic liver disease patients who underwent UGAP, CAP, computed tomography and a liver biopsy on the same day between April 2016 and July 2017. Radiofrequency signals corresponding to the images were compensated by the reference signal previously measured from the uniform phantom with known attenuation (0.44 dB/cm/MHz). The attenuation coefficient was calculated from the signals’ decay slope. The median attenuation coefficient values in patients with S0 (n?=?62), S1 (n?=?63), S2 (n?=?23) and S3 grade (n?=?15) were 0.485, 0.560, 0.660 and 0.720, respectively. Significant correlations were found between attenuation coefficient and percentage steatosis, CAP values and liver-to-spleen computed tomography attenuation ratio (p < 0.001). The areas under the receiver operating characteristic curve of UGAP for identifying ≥S1, ≥S2 and ≥S3 were 0.900, 0.953 and 0.959, respectively, which were significantly better than the results obtained with CAP for identifying ≥S2 and ≥S3. In conclusion, UGAP had high diagnostic accuracy for detecting hepatic steatosis in patients with chronic liver disease     

Involvement of monoamine oxidase-B in the acute neurotoxicity of MPTP in embryonic and newborn mice

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces damage to the nigrostriatal system and subventricular zone (SVZ) of mice. While there have been many researches on the neurotoxicity of MPTP in adult mice, there have been few reports concerning that in embryonic and newborn mice. Very recently, we revealed that such neurotoxicity of MPTP and 1-methyl-4-phenylpyridinium (MPP⁺), a metabolite of MPTP, is observed not only in adult mice but also in embryonic and newborn mice; however, the mechanism of acute toxicity is not well elucidated. In the present study, we attempted to reveal the involvement of monoamine oxidase B (MAO-B) in the metabolism of MPTP to MPP⁺ and dopamine transporter (DAT) in the neuronal cellular uptake of MPP⁺ during the acute toxicity of MPTP in both embryonic and newborn mice. Immunohistochemistry and double-labeling immunofluorescent staining demonstrated an increase of MAO-B-positive glial cells in the brain only in MPTP-treated mice, indicating the involvement of MAO-B in the metabolism of MPTP to MPP⁺ during the acute neurotoxicity of MPTP in both embryonic and newborn mice. The expression of DAT was not observed in the nigrostriatal zone of embryonic mice and in the zone and SVZ of newborn mice. The mechanism of how MPP⁺ is taken up into those neuronal cells remains unknown. In conclusion, MAO-B is involved in the acute neurotoxicity of MPTP in embryonic and newborn mice.     

A longitudinal study for the prediction of the mature acetabular morphology using childhood magnetic resonance imaging

BackgroundAlthough acetabular dysplasia is a common etiology of osteoarthritis of the hip regardless of the history of developmental dysplasia of the hip (DDH), whether or not corrective surgeries are beneficial for the childhood asymptomatic acetabular dysplasia remains controversial due to a lack of evidence. We conducted a longitudinal study to compare the cartilaginous morphology on childhood magnetic resonance imaging (MRI) and the mature hip morphology of the same patient and to assess the predictive indicators for future acetabular dysplasia.MethodsA total of 92 unaffected hips (47 unilateral DDH and 45 unilateral Legg-Calvé-Perthes disease) were reviewed for X-ray and MRI findings on childhood (mean age: 6.0 years) and X-ray findings from a skeletally mature age with a mean follow-up period of 15.1 years. The following parameters were measured and compared: the immature-acetabular index (AI) and center edge angle (CE) on immature X-ray; the cartilage- and bone- AI, CE, Sharp and acetabular head index (AHI) on childhood MRI; and the mature-acetabular roof obliquity (ARO), CE, Sharp and AHI on skeletally mature X-ray. The prognostic factors on childhood MRI for acetabular dysplasia, defined by a CE of <20° on skeletally mature X-ray were also assessed.ResultsPositive correlations were shown between the cartilage-AI and mature-ARO (7.6°/6.3°; r = 0.44), the cartilage-CE and mature-CE (27.8°/28.0°; r = 0.62), the cartilage-Sharp and mature-Sharp (44.4°/41.8°; r = 0.52) and the cartilage-AHI and mature-AHI (78.7%/80.3%; r = 0.46). A multivariate analysis indicated cartilage-CE to be an independent predictor for acetabular dysplasia with a cut-off value of 22°. Children with a cartilage-CE <22° developed more frequently acetabular dysplasia compared to the others (52.4% vs. 1.4%).ConclusionsChildhood MRI findings are useful for the prediction of acetabular dysplasia without a DDH history. Children with a cartilage-CE ≥23° are likely to achieve a non-dysplastic hip without the need for surgical intervention.     

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuroblastic apoptosis in the subventricular zone is caused by 1-methy-4-phenylpiridinium (MPP+) converted from MPTP through MAO-B

Intraperitoneal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration induces apoptosis of subventricular zone (SVZ) doublecortin (Dcx)-positive neural progenitor cells (migrating neuroblasts, A cells). Actually, a metabolite of MPTP, 1-methy-4-phenylpiridinium (MPP⁺), is responsible for neural progenitor cell toxicity. In the present study, to examine whether the MPTP-induced SVZ cell apoptosis is caused directly by MPP⁺ metabolized through monoamine oxidase B (MAO-B), MPTP or MPP⁺ was intracerebroventricularly (icv) injected into C57BL/6 mice. At Day 1 postinjection, many terminal deoxynucleotidyl transferase-mediated dUTP endlabeling (TUNEL)-positive cells were observed in the SVZ of both low (36 μg) and high (162 μg) dose MPTP- and MPP⁺-injected mice. The number of Dcx-positive A cells showed a significant decrease following high dose of MPTP- or MPP⁺-injection on Days 1 and 3, respectively, whereas that of EGFR-positive C cells showed no change in mice with any treatment. In addition, prior icv injection of a MAO-B inhibitor, R(?)-deprenyl (deprenyl), inhibited MPTP-induced apoptosis, but not MPP⁺-induced apoptosis. MAO-B- and GFAP-double positive cells were detected in the ependyma and SVZ in all mice. It is revealed from these results that icv injection of MPTP induces apoptosis of neural progenitor cells (A cells) in the SVZ via MPP⁺ toxicity. In addition, it is suggested that the conversion from MPTP to MPP⁺ is caused mainly by MAO-B located in ependymal cells and GFAP-positive cells in the SVZ.     

Phlebosclerotic colitis that was difficult to distinguish from collagenous colitis

Phlebosclerotic colitis is a rare and recently known disease entity and its etiology is still to be elucidated. Some phlebosclerotic colitis cases are difficult to distinguish from collagenous colitis because of the similarity of pathological findings. In all Japanese case reports of phlebosclerotic colitis in which an association with the use of Chinese herbal medicine is suspected, sansisi (gardenia fruit) was included, suggesting pathogenesis of this disease. We report a case of phlebosclerotic colitis that wasdifficult to be distinguished from collagenous colitis, and an association with the use of Chinese herbal medicine was suspected as the cause of the disease.     

Echographic detection of diethylnitrosamine-induced liver tumors in rats and the effect of the intratumoral injection of an inhibitor of c-Jun N-terminal kinase

Background and Aim:  There have so far been few reports describing echographic studies of chemically-induced carcinogenesis in rodent livers. Using echography, we observed diethylnitrosamine-induced liver tumors in rats and examined the effect of an intratumoral injection of an inhibitor of c-Jun N-terminal kinase.
Methods:  Male Wistar rats were given 100 ppm of diethylnitrosamine for 6 weeks and their liver nodules were examined by echography weekly. The size of the nodules was measured and they were examined histologically. The effect of SP600125, an inhibitor of c-Jun N-terminal kinase, on the growth of rat hepatoma cell line McA-RH7777 was tested in vitro . Thereafter, SP600125 was injected into the liver nodules under echographic guidance in vivo and the changes in the proliferating cell nuclear antigen expression and size of the nodules were examined.
Results:  The four distinct lobes of rat livers were clearly observed by transabdominal echography. The nodules in the livers were first detected 6 weeks after the treatment began, when they were as small as 1.6 mm in diameter. The nodules thereafter became more malignant histologically as they grew larger than 4 mm. SP600125 decreased the expression of proliferating cell nuclear antigen and the growth of McA-RH7777 cells. After SP600125 was injected in vivo , the proliferating cell nuclear antigen level and the growth rate of the rat liver nodules all significantly decreased.
Conclusions:  Our results indicate that echography is quite useful for follow-up studies of liver carcinogenesis in rats, and c-Jun N-terminal kinase might be another therapeutic target in liver neoplasms.