Detection of Alzheimer’s disease-related neuroinflammation by a PET ligand selective for glial versus vascular translocator protein

A substantial and constitutive expression of translocator protein (TSPO) in cerebral blood vessels hampers the sensitive detection of neuroinflammation characterized by greatly induced TSPO expression in activated glia. Here, we conducted in vivo positron emission tomography (PET) and in vitro autoradiographic imaging of normal and TSPO-deficient mouse brains to compare the binding properties of ¹⁸F-FEBMP, a relatively novel TSPO radioligand developed for human studies based on its insensitivity to a common polymorphism, with ¹¹C-PK11195, as well as other commonly used TSPO radioligands including ¹¹C-PBR28, ¹¹C-Ac5216 and ¹⁸F-FEDAA1106. TSPO in cerebral vessels of normal mice was found to provide a major binding site for ¹¹C-PK11195, ¹¹C-PBR28 and ¹⁸F-FEDAA1106, in contrast to no overt specific binding of ¹⁸F-FEBMP and ¹¹C-Ac5216 to this vascular component. In addition, ¹⁸F-FEBMP yielded PET images of microglial TSPO with a higher contrast than ¹¹C-PK11195 in a tau transgenic mouse modeling Alzheimer’s disease (AD) and allied neurodegenerative tauopathies. Moreover, TSPO expression examined by immunoblotting was significantly increased in AD brains compared with healthy controls, and was well correlated with the autoradiographic binding of ¹⁸F-FEBMP but not ¹¹C-PK11195. Our findings support the potential advantage of comparatively glial TSPO-selective radioligands such as ¹⁸F-FEBMP for PET imaging of inflammatory glial cells.     

Cutaneous mastocytosis associated with a mixed germ cell tumour of the ovary: report of a case and review of the literature

A 10-year-old girl with a mixed germ cell tumour of the ovary, treated by surgery and chemotherapy, developed cutaneous mastocytosis approximately 8 months after starting chemotherapy. This is the sixth report of a germ cell tumour associated with mastocytosis. c-kit receptor point mutations, including Asp816Val and Val560Gly were absent in a biopsy specimen obtained from lesional skin.     

Involvement of granulysin-producing T cells in the development of superficial microbial folliculitis

BACKGROUND: Granulysin is a recently identified antimicrobial protein expressed on cytotoxic T cells, natural killer (NK) cells and NKT cells. It has been shown that granulysin contributes to the defence mechanisms against mycobacterial infection. Superficial microbial folliculitis is a common skin disease. In a previous report, we showed that, as a first line of defence, alpha-defensin, a human neutrophil peptide, and beta-defensin (human beta-defensin-2) were expressed in infiltrating neutrophils and in lesional epidermal keratinocytes, respectively, in superficial folliculitis. As we also observed many infiltrating lymphocytes in lesional dermis, we hypothesized that infiltrating lymphocytes may possess antimicrobial substances, such as granulysin, and play a role in the defence mechanism as a second line of defence. OBJECTIVES: Seven specimens of superficial microbial folliculitis diagnosed clinically and histologically were examined by means of immunohistochemistry. To identify the phenotype of cells expressing granulysin, confocal laser microscopic examination was performed. RESULTS: A dense lymphoid cell infiltrate was observed in pustules, in the perivascular regions. A large number of these lymphoid cells were positive for granulysin. Phenotypically, cells consisted of CD3+ T cells, CD8+ T cells and UCHL-1+ T cells. CD20+ cells and CD56+ cells were not observed. Microscopic examination with a confocal laser showed that the lymphocytes producing granulysin were CD3+ and CD4+ T cells but not CD8+ T cells. CONCLUSIONS: We showed that many granulysin-bearing T cells infiltrated affected follicles and perilesional dermis in superficial microbial folliculitis. However, few granulysin-positive lymphoid cells were observed in sterile pustular lesions. Our observations indicated that adaptive immunity such as granulysin, a lymphocyte-produced antimicrobial protein, may play an important role in the cutaneous defence mechanism.     

Histologic bile duct invasion by a mass-forming intrahepatic cholangiocarcinoma

Abstract. Background/Purpose: Although curative surgical resection provides the best chance of long-term survival for patients with intrahepatic cholangiocarcinoma, the presence of bile duct invasion decreases postoperative survival rates in patients with mass-forming intrahepatic cholangiocarcinoma. We carried out this study to determine a surgical strategy for patients with bile duct invasion of these tumors. Methods: Forty-one patients with mass-forming intrahepatic cholangiocarcinoma were classified as either having bile duct invasion (n= 26) or not having bile duct invasion (n= 15). Clinicopathologic findings, including postoperative outcomes, were compared between these two groups. Results: Perineural invasion, lymphatic invasion, and a positive resection margin were more frequent in patients with ductal invasion. Patients with ductal invasion had lower survival rates than those without ductal invasion. Conclusions: Intraoperative frozen section examination of the bile duct stump to confirm a clear resection margin is required in patients with mass-forming tumors. Resection of the extrahepatic bile duct should be considered when tumor cells are identified at the surgical margin of the resected bile duct. Received: October 30, 2001 / accepted: November 16, 2001     

Japanese consensus guidelines for pediatric nuclear medicine

The Japanese Society of Nuclear Medicine has recently published the consensus guidelines for pediatric nuclear medicine. This article is the English version of the guidelines. Part 1 proposes the dose optimization in pediatric nuclear medicine studies. Part 2 comprehensively discusses imaging techniques for the appropriate conduct of pediatric nuclear medicine procedures, considering the characteristics of imaging in children.     

Quantitative assessment of right ventricular function and pulmonary regurgitation in surgically repaired tetralogy of Fallot using 256-slice CT: comparison with 3-Tesla MRI

Objectives

To compare 256-slice cardiac computed tomography (CCT) with cardiac magnetic resonance (CMR) imaging to assess right ventricular (RV) function and pulmonary regurgitant fraction (PRF) in patients with repaired tetralogy of Fallot (TOF).

Methods

Thirty-three consecutive patients with repaired TOF underwent retrospective ECG-gated CCT and 3-Tesla CMR. RV and left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) were measured using CCT and CMR. PRF-CCT (%) was defined as (RVSV???LVSV)/RVSV. PRF-CMR (%) was measured by the phase-contrast method. Repeated measurements were performed to determine intra- and interobserver variability.

Results

CCT measurements, including PRF, correlated highly with the CMR reference (r?=?0.71–0.96). CCT overestimated RVEDV (mean difference, 17.1?±?2.9 ml), RVESV (12.9?±?2.1 ml) and RVSV (4.2?±?2.0 ml), and underestimated RVEF (?2.6?±?1.0 %) and PRF (?9.1?±?2.0 %) compared with CMR. The limits of agreement between CCT and CMR were in a good range for all measurements. The variability in CCT measurements was lower than those in CMR. The estimated effective radiation dose was 7.6?±?2.6 mSv.

Conclusions

256-slice CCT can assess RV function and PRF with relatively low dose radiation exposure in patients with repaired TOF, but overestimates RV volume and underestimates PRF.

Key points

? 256-slice CT assessment of RV function is highly reproducible in repaired TOF. ? Pulmonary regurgitation can be evaluated by biventricular systolic volume difference. ? CT overestimates RV volume and underestimates pulmonary regurgitation, compared with MRI.