Interactions between epithelial and mesenchymal cells in intrahepatic peribiliary glands in normal and hepatolithiatic livers

The anatomy and pathology of the intrahepatic peribiliary glands were evaluated. In this study, we ultrastructuraly examined the peribiliary glands of normal and hepatolithiatic livers using common and serial ultrathin section observations. It is well known that these glands proliferate markedly in hepatolithiasis. These glands were composed of several acini surrounded by thickened and multilayered basement membranes, and there were mesenchymal cells (the majority were fibroblasts) in the periacinar fibrous connective tissue. Some cytoplasmic processes of acinar epithelial cells and mesenchymal cells in the periacinar connective tissue were in close contact with each other within the thickened and multilayered basement membranes. Such cell-to-cell interaction was most frequent in cases of hepatolithiasis, in which peribiliary glands proliferated markedly. In hepatolithiatic livers, some unmyelinated nerve fibers or axonal button profiles were in close contact with periacinar mesenchymal cells and also with cytoplasmic processes of glandular epithelial cells. Such contacts were rare in normal livers. These findings suggest that such epithelial and mesenchymal cell interactions and innervations play a part in the normal regulation of peribiliary glands and also in the proliferation of peribiliary galnds in hepatolithiasis.     

Loss of heterozygosity on chromosomes 3, 13, and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung.

By a molecular genetic approach using polymorphic DNA markers that detect allelic deletion of specific chromosomal regions, we analyzed for possible loss of chromosomal heterozygosity in five different histological types of lung cancers obtained from 47 patients. In small-cell carcinomas, the incidence of allelic deletions at three different chromosomal loci was extremely high; loss of heterozygosity was detected on chromosomes 3p in 7 of 7 patients (100%), 13q in 10 of 11 patients (91%), and 17p in 5 of 5 patients (100%). The deletions at these loci in small-cell carcinomas were observed even in the tumors without any clinical evidence of metastasis. Furthermore, loss of heterozygosity on chromosomes 3p and 13q occurred prior to NMYC amplification and chromosome 11p deletion. Loss of heterozygosity on chromosome 3p was also detected with high frequency in adenocarcinomas [5 of 6 patients (83%)]. Heterozygosity of chromosomes 13q and 17p was lost in 10 of 31 patients (32%) and in 3 of 12 patients (25%), respectively, of lung cancers other than small-cell carcinomas. These results indicate that recessive genetic changes involving sequences on chromosomes 3p, 13q, and 17p may play important roles in the genesis of small-cell carcinoma, and those on chromosome 3p may play an important role in the genesis of adenocarcinoma.     

IL-18 and IL-12 induce intestinal inflammation and fatty liver in mice in an IFN-gamma dependent manner

BACKGROUND: In murine models of inflammatory bowel disease, colonic inflammation is considered to be caused by an aberrant Th1-type immune response. AIM: To investigate if systemic administration of interleukin (IL)-12 and IL-18 to wild-type BALB/c mice induces liver injury and intestinal inflammation, and if pathological changes are observed, what cytokines are involved. METHODS: Mice (BALB/c-wild-type (wt), MRL-lpr/lpr, BALB/c-interferon gamma knock out (IFN-gamma KO), C57BL/6-inducible nitric oxide synthase (iNOS) KO, and BALB/c tumour necrosis factor alpha (TNF-alpha) KO) were injected intraperitoneally each day with IL-12 (20 ng/g/mouse) and/or IL-18 (200 ng/g/mouse). RESULTS: Administration of IL-12 and IL-18 to BALB/c-wt mice induced prominent intestinal mucosal inflammation and fatty liver, leading to piloerection, bloody diarrhoea, and weight loss. IL-12 and IL-18 induced striking elevations in serum levels of IFN-gamma that caused NO production, although increased NO had no exacerbating effect on mice. Moreover, iNOS KO mice, or MRL lpr/lpr mice lacking functional Fas were equally susceptible to IL-12 and IL-18. Administration of IL-12 and IL-18 did not induce TNF-alpha production in wild-type mice, and the same treatment to TNF-alpha KO mice induced intestinal mucosal inflammation. Furthermore, they had diffuse and dense infiltration of small fat droplets in their hepatocytes associated with an increase in serum levels of liver enzymes. In contrast, the same treatment in IFN-gamma KO BALB/c mice and iNOS KO mice did not induce these changes. CONCLUSIONS: Our study strongly indicates that IL-18 together with IL-12 induces intestinal mucosal inflammation in an IFN-gamma dependent but TNF-alpha, NO, and Fas ligand independent manner, and fatty liver is dependent on IFN-gamma and NO.     

Role of c-kit receptor tyrosine kinase-mediated signal transduction in proliferation of bile epithelial cells in young rats after ligation of bile duct: a study using Ws/Ws c-kit mutant rats

BACKGROUND/AIMS: Recently, it has been shown that the c-kit receptor tyrosine kinase (KIT) is expressed in the liver of young rats, and its expression is up-regulated in bile epithelial cells (BEC) after ligation of the common bile duct (BDL). To clarify a role of KIT in BEC, we examined whether BEC of Ws/Ws rats, whose KIT kinase activity was severely impaired, could proliferate in response to bile stasis after BDL. METHODS/RESULTS: When 2-week-old control normal (+/+) and Ws/Ws mutant rats underwent BDL, only a few BEC were found in the portal field of livers of Ws/Ws rats, whereas many BEC were found in that of +/+ rats. Furthermore, Ki-67 immunostaining showed that the proliferative activity of BEC in 2-week-old Ws/Ws rats was much lower than that in +/+ rats of the same age. In contrast, when 6-week-old +/+ and Ws/Ws rats underwent BDL, BEC similarly proliferated in the livers of +/+ and Ws/Ws rats, and the proliferative activity of BEC was comparable. CONCLUSIONS: The mechanism whereby BEC proliferate in response to bile stasis after BDL may be different between 2- and 6-week-old rats, and KIT mediated-signal transduction plays a crucial role in the proliferation of immature BEC in young rats.     

A case of asymptomatic racemose hemangioma treated by bronchial artery embolization]

A 69-year-old man had an abnormal shadow on chest X-ray and bronchoscopic examination showed that left B4 was completely occluded by a tumor. A non-pulsatile polypoid nodule was also found in right B'. The tumor in the left B4 was diagnosed as carcinoid, but the nodule in right B' was suspected to be hemangioma and biopsy was not performed. Bronchial arteriography revealed hypervascularization with dilated vessels distributing to the lingular lobe and convoluted and a dilated bronchial artery extending to the right upper lobe. From these findings, we diagnosed racemose hemangioma of the bronchial artery of the right upper lobe. After bronchial artery embolization of the right and left bronchial arteries, he underwent segmentectomy of the lingula and was discharged without complications. Two months after the operation, bronchoscopic examination showed that the racemose hemangioma had shrunk and the swelling in the surrounding mucosa had decreased. If a submucosal small nodule is observed during bronchoscopy, biopsy should be performed after bronchial arteriography, and if the nodule is diagnosed as racemose hemangioma, bronchial artery embolization should be performed.     

Rectal submucosal tumor-like lesion originating from intestinal tuberculosis

We present the case of a 55-year-old man who underwent transsacral local excision for a rectal submucosal tumor-like lesion suspected to originate from tuberculosis. The lesion, 2 cm in size, was found incidentally in the posterior wall of the lower rectum during anal fistulectomy. The lesion was apart from the primary crypt of the anal fistula. Barium enema and colonoscopy revealed a protuberant submucosal growth with a shallow depression of the overlying mucosa. Although computed tomography and magnetic resonance imaging showed a well defined round mass within the rectal wall, digital rectal examination suggested extramural origin. Since repeated endoscopic biopsies were negative, we selected the transsacral approach for excisional biopsy to achieve histological diagnosis. The lesion was confined to the rectal wall and the full-thickness rectal wall was excised. Histologically, a foreign-body granuloma with acute inflammation was the main component of the lesion. Caseating granulomas and Langhans' giant cells, consistent with tuberculosis, were also found.     

Genetic Characterization of Coronaviruses from Domestic Ferrets,Japan

We detected ferret coronaviruses in 44 (55.7%) of 79 pet ferrets tested in Japan and classified the viruses into 2 genotypes on the basis of genotype-specific PCR. Our results show that 2 ferret coronaviruses that cause feline infectious peritonitis–like disease and epizootic catarrhal enteritis are enzootic among ferrets in Japan.     

Non-enhanced magnetic resonance angiography can evaluate restenosis after carotid artery stenting with the Carotid Wallstent

Background

Carotid artery stenting (CAS) requires follow-up imaging to assess in-stent restenosis (ISR). This study aimed to determine whether non-enhanced magnetic resonance angiography (NE-MRA) is useful for evaluating ISR.

Method

Between 2009 and 2013, we performed 118 consecutive CAS procedures using the Precise stent (n?=?78) and the Carotid Wallstent (n?=?40). We reviewed 1.5 T NE-MRA and examined visualization of the stent lumen and the degree of ISR if present. Other imaging modalities were used as references.

Results

NE-MRA performed just after CAS was not able to visualize the stent lumen in all patients because of metal artifacts. In the Carotid Wallstent group, follow-up NE-MRA was available in 22 patients. The stent lumen was visible more than three months after CAS in all patients. Among them, >40 % ISR was observed by other modalities in eight lesions. The degree of restenosis measured by NE-MRA (y%) had a linear relationship with that measured by conventional angiography (x%) (y?=?0.97x-0.4, r?=?0.79, P?=?0.021). In one case among 17 without ISR (6 %), NE-MRA showed false ISR. In the Precise stent group, NE-MRA did not visualize the stent lumen in the follow-up period.

Conclusions

NE-MRA can visualize the stent lumen in the Carotid Wallstent more than three months after CAS, but not in the Precise stent at follow-up. This delayed visualization might depend on endothelialization of the stent lumen. The degree of ISR measured by NE-MRA is comparable to that by conventional angiography. NE-MRA can evaluate ISR after CAS with the Carotid Wallstent (100 % sensitivity and 94 % specificity).     

Basal cell adenocarcinoma of the parotid gland: Comparison with basal cell adenoma for preoperative diagnosis

ObjectiveTo summarize the diagnosis and treatment outcomes of basal cell adenocarcinoma (BCAC) of the parotid gland, a rare low-grade malignancy, at a single institution, and to investigate the treatment approach for this rare malignancy.MethodsWe conducted a retrospective analysis of 9 patients with BCAC during 20 years from September 1999 to December 2019. Forty-five patients with basal cell adenoma (BCA), who were treated during the same time period, were used for comparison. The clinical characteristics of BCAC, diagnostic imaging, the usefulness of fine-needle aspiration cytology (FNAC) and frozen section biopsy (FSB), histological assessment of malignancy, and treatment outcomes were investigated.ResultsThere were no marked differences in sex, age, tumor diameter, or tumor location between BCAC and BCA cases. Among the 9 patients with BCAC, one patient was noted with pain/tenderness, and two patients were observed with adhesion to the surrounding tissues. Only one patient was diagnosed as malignant based on MRI/US. FNAC for BCAC was suspicious for malignancy in 6 of the 9 cases, which included one patient with the correct grade of malignancy, one patient with malignancy only, and 4 patients suspicious for malignancy. FSB was suspicious for malignancy in 8 of the 9 cases. Malignancy grade was determined based on infiltration to the surrounding tissues and expression of Ki-67, p53, and bcl-2. One patient with infiltration to the surrounding tissue was diagnosed as intermediate-grade malignancy, while the remaining 8 patients were diagnosed as low-grade malignancy. The BCAC cases included 7 patients with T2 and 2 patients with T1. Conservative resection was performed for all patients, and all cases are surviving cancer-free.ConclusionThe malignancy of BCAC can be suspected before surgery based on symptoms/signs, diagnostic imaging, and FNAC. FSB enables the diagnosis of not only malignancy but also the grade of malignancy, which may help determine the appropriate surgical resection. Although all 9 patients with BCAC are surviving free from cancer, a long-term follow-up is warranted.