Imaging of acquired cystic disease-associated renal cell carcinoma by contrast-enhanced ultrasonography with perflubutane microbubbles and positron emission tomography-computed tomography.

The preoperative assessment of renal cell carcinoma (RCC) complicated with acquired renal cystic disease in a 63-year-old male patient on long-term hemodialysis (30 years and 8 months) that was difficult because of no or poor contrast enhancement by dynamic CT scan is reported. Contrast-enhanced ultrasonography with perflubutane microbubbles and positron emission tomography-computed tomography (PET-CT) with 18F-fluorodeoxy glucose (FDG) in addition to dynamic CT were effective and useful for preoperative assessment of this patient. The pathological subtype of RCC in this patient was acquired cystic disease-associated RCC (ACD-associated RCC), which has been newly defined by Tickoo et al. (Am J Surg Pathol 30:141-153, 2006).

Long-term natural history of acquired cystic disease of the kidney.

Patients with acquired cystic disease of the kidney (ACDK) were followed longitudinally over an average of 21.7 +/- 5.4 years to determine the natural history of the disease; that is, how big the kidneys become, when the kidney size reaches a plateau, and when the size regresses. Twenty-seven male and 20 female patients with chronic glomerulonephritis treated at our hospital were investigated. CT scans were performed once a year and kidney volume was measured. Two different quadratic curves with a node of 5.2 years for males and 2.5 years for females after the start of hemodialysis were fitted to log-transformed kidney volume to the duration of hemodialysis using a linear mixed model. The maximum kidney volume in male patients was obtained 21.1 years after the start of hemodialysis using this model. Peak values of kidney volume were demonstrated in 19 of 26 cases during the observation period. The median peak value (interquartile range) of bilateral kidney volumes was 274 (165-849) mL/1.73 m(2) occurring 19.1 +/- 4.5 years after the start of dialysis. In one male patient who had undergone nephrectomy due to renal cell carcinoma and in two of the remaining 26 male patients, the maximum kidney volume of 782 (residual kidney), 1151, and 1129 mL regressed to 428, 616, and 847 mL (reduction rate: 45.3, 46.5, and 25.0%) at 20.6, 25.4, and 23.1 years after the start of hemodialysis, respectively. Kidney enlargement due to ACDK reached a plateau after 21.1 years of hemodialysis in the male patients. Partial regression of severe ACDK may occur naturally after long-term hemodialysis without renal transplantation.

Genomic organization, chromosomal localization, and promoter of human gene for FK506-binding protein 12.6.

Cyclic ADP-ribose (cADPR) induces the release of Ca2+ from microsomes of pancreatic islets for insulin secretion. It has been demonstrated that cADPR binds to FK506-binding protein 12.6 (FKBP 12.6) on rat islet ryanodine receptor and that the binding of cADPR to FKBP12.6 frees the ryanodine receptor from FKBP12.6, causing it to release Ca2+ [Noguchi, N., Takasawa, S., Nata, K., Tohgo, A., Kato, I., Ikehata, F., Yonekura, H., Okamoto, H., 1997. Cyclic ADP-ribose binds to FK506-binding protein to release Ca2+ from islet microsomes. J. Biol. Chem. 272, 3133-3136.]. In this study, we cloned, characterized the structural organization of the human FKBP12.6, which is highly homologous to human FKBP12, and analyzed the promoters for FKBP12.6 and FKBP12. Human FKBP12.6 gene spanned about 16 kb in length and consisted of four exons and three introns. The positions of exon-intron junction of the FKBP12.6 gene were perfectly matched with those of FKBP12 gene except that FKBP12 has an additional exon, exon V, to code exclusively for 3'-UTR. Fluorescence in situ hybridization revealed that the FKBP12.6 gene was located on chromosome 2 p21-23, which is different from the locus (chromosome 20 p13) of the FKBP12 gene. Reporter gene analyses revealed that the regions of -58 approximately -24 of FKBP12.6 and -106 approximately -79 of FKBP12 are important for promoter activities. The promoters contain a consensus transcription factor binding sequence for Sp family in FKBP12.6 and Ets-1 in FKBP12. Electrophoretic mobility shift assays showed that nuclear proteins bind to the promoters. The DNA/protein complex on FKBP12.6 promoter was competed out by Sp1 consensus probe and the complex was supershifted by anti-Sp3 antibodies. On the other hand, the DNA/protein complex on FKBP12 promoter was competed out by Ets-1 consensus probe but not by its mutant probe, indicating that Sp3 and Ets-1 play an essential role in transcription of FKBP12.6 and FKBP12, respectively.

Prevention of lymphocytic thyroiditis in iodide-treated non-obese diabetic mice lacking interferon regulatory factor-1.

OBJECTIVE: Interferon regulatory factor-1 (IRF-1) is a critical regulator of interferon-gamma(IFNgamma)-mediated immune responses. To determine whether IRF-1 is involved in the pathogenesis of thyroiditis in animal models, we evaluated the incidence of iodide-induced lymphocytic thyroiditis (LT) in non-obese diabetic (NOD) mice lacking IRF-1 as well as IRF-1 +/+ and +/- mice. DESIGN: IRF-1 +/+, +/- and -/- NOD mice at 6 weeks of age were fed water (group 1) or iodide water (group 2) for 8 weeks. METHODS: Thyroids were examined histopathologically and intrathyroidal lymphocytic infiltration was arbitrarily graded. Serum thyroxine (T(4)) and anti-mouse thyroglobulin antibody (anti-mTgAb) levels were measured. Spleen cell population was analyzed by flow cytometry, and IFNgamma and interleukin-10 produced by splenocytes were measured by enzyme-linked immunosorbent assay. RESULTS: In group 1, only 4.3% of NOD mice developed LT. In contrast, 67.6% of mice in group 2 developed the disease. Iodide treatment induced LT in more than 80% of IRF-1 +/+ and +/- mice. However, no IRF-1 -/- mice in group 2 developed LT. There was no difference in both serum anti-mTgAb and T(4) levels among the three IRF-1 genotypes of NOD mice. Numbers of splenic CD8(+) T cells and IFNgamma production by Concanavalin A-stimulated splenocytes were markedly decreased in IRF-1-deficient NOD mice. CONCLUSIONS: IRF-1 is involved in the development of iodide-induced LT in NOD mice.

Association between duration of daily VDT use and subjective symptoms.

BACKGROUND: Although visual display terminal (VDT) work has become a common task among office workers, surveys which would help to determine the allowable duration of daily VDT use are limited. METHODS: We investigated more than 25,000 workers three times over a 3-year period using a self-administered questionnaire. Three factors, namely mental, physical and sleep-related symptoms, were extracted by factor analysis. Adjusted means of each factor score were compared with the duration of daily VDT use by general linear model. RESULTS: Physical symptoms score became higher with increasing duration of daily VDT use without a threshold effect. Mental and sleep-related symptom scores of the workers using VDT for more 5 hr/day were significantly higher than that of the groups using VDT for >1, 1-3, and 3-5 hr/day. CONCLUSIONS: Duration of daily VDT use was linearly related to the physical symptom score, and was non-linearly related to mental and sleep-related symptom score with a threshold effect of 5 hr/day.