Clinical Potential of Digital Linear Tomosynthesis Imaging of Total Joint Arthroplasty

The present study was performed to evaluate the potential for clinical application of digital linear tomosynthesis in imaging hip prostheses. Volumetric x-ray digital linear tomosysnthesis was used to image hip prostheses. The tomosynthesis was compared to metal artifact reduction (MAR) computed tomography (CT), and non-MAR CT scans of a prosthesis case. The effectiveness of this method in enhancing visibility of a prosthesis case was quantified in terms of the signal-to-noise ratio (SNR), and removal of ghosting artifacts in a prosthesis case was quantified in terms of the artifact spread function (ASF). In the near in-focus plane, the contrast is greater in the MAR CT or tomosynthesis relative to the non-MAR CT. The order of ASF performance of the algorithm was as follows: (1) tomosynthesis; (2) MAR-CT; (3) non-MAR CT. The potential usefulness of digital linear tomosynthesis for evaluation of hip prostheses was demonstrated. Further studies are required to determine the ability of digital linear tomosynthesis to quantify the spatial relationships between the metallic components of these devices as well as to identify bony changes with diagnostic consequences.     

Malignant transformation of mature cystic teratoma to squamous cell carcinoma involves altered expression of p53‐ and p16/Rb‐dependent cell cycle regulator proteins

Ovarian mature cystic teratomas (MCT) uncommonly undergo malignant transformation to squamous cell carcinoma (SCC). While alterations in the p53 tumor suppressor gene and protein have been shown, few studies have analyzed other molecular changes leading to this malignant conversion. The purpose of the present study was to investigate 21 samples of SCC arising in MCT for altered expression in known p53‐ and p16/Rb‐dependent cell cycle regulatory proteins, and the association between their expression and cellular proliferation and histological features. Overexpression of the p53 protein was observed in 14 SCC (67%), while four (19%) had point mutations in the p53 gene. Reduced expression of the p16 protein was observed in 18 SCC (86%), while p16 gene alterations (hypermethylation (29%) and point mutation (33%)) were found in 11 (52%). Furthermore, a statistically significant correlation was observed between p53 and Rb overexpression (P = 0.0010), and the overexpression of both p53 and Rb was respectively significantly correlated with increased cellular proliferation. The results indicate that alterations in both the p53 and p16‐Rb pathways are associated with SCC arising in MCT.     

An Experimental Comparison of Flat-Panel Detector Performance for Direct and Indirect Systems (Initial Experiences and Physical Evaluation)

The purpose of this work was to compare direct and indirect detectors in terms of their system linearity, presampled modulation transfer function (MTF), Wiener spectrum (WS), noise equivalent quanta (NEQ), and power spectrum. Measurements were made on two flat-panel detectors, GE Revolution XR/d (indirect) and Shimadzu Safire (direct) radiographic techniques. The system linearity of the systems was measured using a time-scale method. The MTF of the systems was measured using an edge method. The WS of the systems was determined for a variable range of exposure levels by two-dimensional Fourier analysis. The NEQ was assessed from the measured MTF, WS, and estimated ideal signal-to-noise ratios. Power spectrum analyzed the chest phantom within artificial lesions. System linearity was excellent for the direct systems. For the direct system, the MTF was found to be significantly higher than that for the indirect systems. For the direct system, the WS was relatively uniform across all frequencies. In comparison, the indirect system exhibited a drop in the WS at high frequencies. At lower frequencies, the NEQ for the indirect system was noticeably higher than for the direct system. Power spectrum for the direct system was relatively flat and similar to that for white noise. The indirect system exhibited significant reduction at high spatial frequencies. In general, the direct systems exhibit improved image quality over indirect systems at comparable exposure dose.     

Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice

Mice that lack the p85alpha regulatory subunit of phosphatidylinositol-3 kinase (PI3K) are deficient in gastrointestinal and peritoneal mast cells but have dermal mast cells. Accordingly, these mice show impaired bacterial clearance in response to acute septic peritonitis and are highly susceptible to infection by the intestinal nematode Strongyloides venezuelensis. Systemic anaphylactic shock responses, however, are intact. We found that although reconstitution of PI3Kminus sign/minus sign mice with bone marrow--derived mast cells (BMMCs) restored anti-bacterial immunity, only T helper type 2 (TH2)-conditioned BMMCs, not "standard" BMMCs, were able to restore anti-nematode immunity. This finding highlights the importance of the TH2 response in the control of nematode infection. Thus, PI3K likely plays an essential role in host immune responses by regulating both the development and induction of mast cells.     

Three novel mutations of the fibrillin-1 gene and ten single nucleotide polymorphisms of the fibrillin-3 gene in Marfan syndrome patients

Marfan syndrome (MFS) is an autosomal dominant disorder of the extracellular matrix. Allelic variations in the gene for fibrillin-1 (FBN1) have been shown to cause MFS. To date, over 550 mutations have been identified in patients with MFS and related connective tissue diseases. However, about a half of MFS cases do not possess mutations in the FBN1 gene. These findings raise the possibility that variants located in other genes cause or modify MFS. To explore this possibility, firstly we analyzed FBN1 allelic variants in 12 Japanese patients with MFS, and secondly we analyzed fibrillin-3 gene (FBN3) in patients without FBN1 mutations using conformation sensitive gel electrophoresis (CSGE) and direct sequencing analysis. We identified three novel FBN1 mutations and ten FBN3 single nucleotide polymorphisms (SNPs). In this report, we could not detect a responsible mutation of the FBN3 gene for MFS. Although the number of the cases in this report is small, at least these results suggest that disease-causing mutations in exon regions of the FBN3 gene are very rare in MFS.Nucleotide sequence data reported are available in the DDBJ/EMBL/GenBank databases under the accession numbers: AB177797, AB177798, AB177799, AB177800, AB177801, AB177802, AB177803     

Characterization of factor XII Tenri, a rare CRM-negative factor XII deficiency

Factor XII Tenri (Y34C), a rare cross-reacting material (CRM)-negative factor XII deficiency, was identified in a 71-yr-old Japanese woman with angina pectoris. In the patient's plasma, factor XII activity and antigen levels were only 1.6% and 5.0%, respectively, of those seen in a normal subject. Immunoblot analysis showed that the secreted factor XII Tenri existed not only as a monomer (76 kDa), but also in complexes with apparent molecular weights of approximately 115, 140, 190, 215, and 225 kDa. After reduction with 2-mercaptoethanol, the factor XII Tenri contained in the complexes was completely converted to monomeric form on immunoblot patterns. It appeared that some of the secreted factor XII Tenri formed several types of disulfide-linked complexes, including a factor XII-alpha1-microglobulin complex, through a newly generated Cys residue. The monomeric form of factor XII Tenri, like normal factor XII, was degraded into 2 major fragments with molecular weights of approximately 45 kDa and 30 kDa following mixing with activated partial-thromboplastin-time measuring reagent (cephalin and ellagic acid), whereas the factor XII Tenri that formed the complexes was not. This indicates that the factor XII Tenri present in disulfide-linked complexes with other proteins (and itself) is not converted to active forms, suggesting that attached proteins obstruct or delay the activation of factor XII via an inhibition of its binding to a negatively charged surface in vitro.     

Elevated expression of E-cadherin and α-, β-, and γ-catenins in metastatic lesions compared with primary epithelial ovarian carcinomas

E-cadherin and catenins play key roles in cell adhesion and motility. Little is known about the changes in expression of these molecules in the progression of ovarian carcinomas. In the present study, the immunohistochemical expression of E-cadherin and α-, β-, and γ-catenins was examined in 77 cases of ovarian carcinoma. In addition, the expression of these molecules was evaluated in 26 matched pairs of primary and metastatic lesions of advanced ovarian carcinomas. Of the 77 primary lesions, positive staining for E-cadherin and α-, β-, and γ-catenin was observed in 75 (97%), 63 (82%), 71 (92%) and 57 (74%) cases, respectively. Positivity for E-cadherin and α-, β-, and γ-catenin was significantly decreased in stage III and IV tumors compared with stage I and II tumors, suggesting that expression of the cadherin-catenin complex is reduced with the advancing stages of a tumor. Interestingly, expression of E-cadherin and α-, β-, and γ-catenin in the lesions of peritoneal dissemination was significantly increased compared with the primary lesions. These findings suggest that expression of the cadherin-catenin complex changes markedly and that reexpression may occur during the peritoneal dissemination of ovarian carcinoma cells.     

Expression of BRCA1 protein in benign, borderline, and malignant epithelial ovarian neoplasms and its relationship to methylation and allelic loss of the BRCA1 gene

BRCA1 is a putative tumour suppressor gene responsible for a hereditary ovarian cancer syndrome. To clarify the possible involvement of BRCA1 in the development of sporadic ovarian neoplasms, this study analysed the immunohistochemical expression of BRCA1 protein in normal ovarian surface epithelium and 119 epithelial ovarian tumours (19 benign, 24 borderline, and 76 malignant tumours). Loss of heterozygosity (LOH) of BRCA1 was examined using three microsatellite markers to analyse the relationship between BRCA1 expression and alterations of the BRCA1 gene. Methylation of the BRCA1 promoter was also analysed by methylation-specific PCR. In ovarian carcinomas showing heterogeneous expression of BRCA1 protein in the same tumour, LOH and methylation status were analysed using microdissection techniques. Finally, the relationship of BRCA1 expression or its genetic alteration to clinicopathological parameters and patient survival was analysed. Ovarian surface epithelial cells expressed BRCA1 protein. Decreased expression of BRCA1 was found in 16% of benign tumours, 38% of borderline tumours, and 72% of carcinomas. LOH of BRCA1 was demonstrated in no benign tumours, 15% of borderline tumours, and 66% of carcinomas. Methylation of BRCA1 was not detected in benign or borderline tumours, but was present in 31% of carcinomas. Reduced expression of BRCA1 correlated with the presence of gene methylation. The frequency of BRCA1 methylation and LOH was higher in serous carcinomas than in other types. In one of the three serous carcinomas that showed heterogeneous expression of BRCA1, BRCA1-positive borderline-like tumour cells were LOH-positive and methylation-negative, whereas adjacent BRCA1-negative carcinoma cells were LOH-positive and methylation-positive. The prognosis of carcinoma patients did not correlate with BRCA1 expression or genetic status. These findings suggest that reduced expression of BRCA1 protein along with genetic and epigenetic changes of the BRCA1 gene play an important role in the development of sporadic ovarian carcinomas, particularly those of serous histology.     

Melanocytes and melanosis of the oesophagus in Japanese subjects — analysis of factors effecting their increase

Summary Normal oesophagus specimens taken from 65 autopsy cases and surgical specimens from 127 oesophageal carcinoma cases were examined histopathologically to determine melanocyte incidence and distribution. Melanocytes were found in the epithelio-stromal junction in 7.7% of normal oesophagus specimens examined at autopsy, and in 29.9% of surgical cases with oesophageal carcinoma. Positive specimens in the latter groups, especially from pre-operatively irradiated individuals, showed a more remarkable increase of melanocytes than was evident in any of the normal oesophageal samples. There were no significant differences in incidence between males and females, or between age groups. In cases where the cancer invaded into deeper stroma, the melanocytes were mainly observed in the normal epithelium around the carcinomas. Epithelial and stromal elements of the melanotic mucosa commonly showed hyperplastic changes such as acanthosis or basal cell hyperplasia, and chronic oesophagitis. Melanocytes were observed most commonly in the lower part of the oesophagus, the site where malignant melanoma of the oesophagus, most often originates. These results strongly suggest that the melanocyte increase observed in areas of hyperplastic epithelium and chronic oesophagitis may play an important role as a precursor lesion for malignant melanoma in the oesophagus.