Renal cell carcinoma in patients with end-stage renal disease: relationship between histological type and duration of dialysis.

OBJECTIVE: To evaluate the clinical outcomes and histological types of renal cell carcinoma (RCC) arising in patients with end-stage renal disease (ESRD), and to analyse the relationship of histopathological features with the duration of dialysis. PATIENTS AND METHODS: Clinical characteristics and outcomes of 34 patients who had a radical nephrectomy for RCC arising in ESRD between November 1994 and June 2008 were investigated. Archive paraffin-embedded tissue specimens obtained from 27 patients were histochemically and immunohistochemically analysed to determine the histopathological type. RESULTS: There was one death from cancer and one patient with local progression within a median observation period of 29.5 months. Acquired cystic disease (ACD)-associated RCC, clear cell-papillary RCC, mucinous tubular and spindle-cell carcinoma, and Xp11.2 translocation/TFE3 gene fusion were identified in eight, two, three and one patient, respectively. Conventional clear-cell RCC was the predominant histological type (nine of 15) in patients with a duration of dialysis of <10 years, while ACD-associated RCC was predominant (seven of 12) in those with dialysis for > or =10 years. Sarcomatoid foci were identified in three patients with dialysis for > or =10 years. Papillary adenoma was microscopically identified as a satellite tumour in 10 patients. CONCLUSION: The spectrum of histological types of RCCs arising in ESRD is distinct from that of sporadic RCCs. Patients with a longer duration of dialysis should have particular attention for progression and metastasis. Immunohistochemical profiling is efficient in the histological classification of RCCs arising in ESRD, although knowledge about genetic changes remains to be accumulated.

Influence of inflammation and aging on macrophage inhibitory cytokine-1 gene expression in rat ventral prostate.

OBJECTIVES: We have previously reported that the macrophage inhibitory cytokine-1 (MIC-1) gene is downregulated in human symptomatic benign prostatic hyperplasia. The aim of this study was to investigate the histologic changes and MIC-1 gene expression in the prostate of young nonbacterial prostatitis model (Y-NBP) and aging rats. METHODS: A total of 35 Wistar male rats, 13 weeks old, were castrated and subjected to (a) castration alone for 14 days, (b) Y-NBP-14d (0.25 mg/2 mL/kg beta-estradiol injection for 14 days), or (c) Y-NBP-30d (beta-estradiol injection for 30 days). A total of 5 male rats, 10 months old, were also analyzed. We used 21 male rats, 13 weeks old, who had undergone sham surgery as the controls. The ventral lobes of the prostate were histologically examined with Masson's trichrome staining or immunostaining using an anti-macrophage antibody. The MIC-1 mRNA levels were quantitatively assessed using real-time reverse transcriptase-polymerase chain reaction. RESULTS: The MIC-1 gene mRNA levels in the castration alone, Y-NBP-14d, and Y-NBP-30d rat prostates were greater than those in the control rats (P < .005). In contrast, those of the 10-month-old rats were lower than those of the controls (P = .0093). The mean stroma-to-epithelium ratio in the Y-NBP-30d rats, 10-month-old rats, and 13-week-old controls was 1.28, 0.26, and 0.10, respectively (Y-NBP-30d vs 10-month-old rats, P = .0008; 10-month-old vs 13-week-old rats, P = .001). The number of infiltrating macrophages in the Y-NBP-14d, Y-NBP-30d, and 10-month-old rats was greater than that of the 13-week-old controls (P < .001). CONCLUSIONS: Castration causes induction of MIC-1 gene expression. Estradiol treatment has little effect on MIC-1 gene expression but causes a significant increase in the stroma-to-epithelium ratio. The aging rat prostate is more similar to human benign prostatic hyperplasia than is the Y-NBP model in light of MIC-1 gene expression and histologic changes.

[Assessment of the urinary status by self-administered questionnaires in men after radical prostatectomy-- comparison with the urination status of elderly women].

The lower urinary tract anatomy in men after radical prostatectomy (RP) resembles that in women. Out of 112 male patients who had undergone RP for localized prostate cancer, 102 (91%) of them responded to a questionnaire survey. The mean age of the responders at the time of RP was 65.9 +/- 5.3 years. The time of response after RP ranged from 2 months to 6 years (median: 44 months). The instruments used for the assessment of urinary status were the International Prostate Symptom Score (IPSS) and QOL score, the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and Overactive Bladder Symptom Score (OABSS). Urinary status of 40 elderly female patients aged 59.5 +/- 6.9 years who consulted our outpatient clinic due to conditions (microhematuria, simple renal cyst, etc.) unrelated to lower urinary tract disorders were assessed with the IPSS. In the male patients, total IPSS and QOL score showed significant improvement over time after RP (P = 0.0004, P = 0.0015, respectively). In particular, the voiding symptom score of IPSS showed significant improvement (P < 0.0001). The improvement of incontinence within 1 year after RP was confirmed with ICIQ-SF (p = 0.06). In contrast, the storage symptom score of IPSS after RP was not different with time after RP. Furthermore, the OABSS rose with time after RP (p = 0.08). On the other hand, in the elderly female controls, the storage symptom score of IPSS was significantly higher than voiding symptom score (P = 0.0019). Men who underwent RP showed significant improvement in their voiding symptoms and continence status, but the storage symptoms, progressively worsened following RP. Consequently, careful follow-up and appropriate medical intervention are needed in men after RP as in aging women.

[Temporary inferior vena cava filter applied to 4 patients with urological disease].

A temporary inferior vena cava (IVC) filter was placed in 4 patients. Patient 1 had an advanced testicular germ cell tumor with IVC tumor thrombosis, patient 2 presented with a large adrenal tumor with IVC tumor thrombosis, patient 3 was found to have deep vein thrombosis following grade 3b renal injury, and patient 4 was suffering severe SLE with renal vein thrombosis. The temporary inferior vena cava filter prevented pulmonary thromboembolism in all cases, and no adverse reaction was observed. Temporary inferior vena cava filter is safe and useful to prevent pulmonary thromboembolism associated with urological disorders.

Protection against fatty liver but normal adipogenesis in mice lacking adipose differentiation-related protein.

Adipose differentiation-related protein (ADFP; also known as ADRP or adipophilin), is a lipid droplet (LD) protein found in most cells and tissues. ADFP expression is strongly induced in cells with increased lipid load. We have inactivated the Adfp gene in mice to better understand its role in lipid accumulation. The Adfp-deficient mice have unaltered adipose differentiation or lipolysis in vitro or in vivo. Importantly, they display a 60% reduction in hepatic triglyceride (TG) and are resistant to diet-induced fatty liver. To determine the mechanism for the reduced hepatic TG content, we measured hepatic lipogenesis, very-low-density lipoprotein (VLDL) secretion, and lipid uptake and utilization, all of which parameters were shown to be similar between mutant and wild-type mice. The finding of similar VLDL output in the presence of a reduction in total TG in the Adfp-deficient liver is explained by the retention of TG in the microsomes where VLDL is assembled. Given that lipid droplets are thought to form from the outer leaflet of the microsomal membrane, the reduction of TG in the cytosol with concomitant accumulation of TG in the microsome of Adfp-/- cells suggests that ADFP may facilitate the formation of new LDs. In the absence of ADFP, impairment of LD formation is associated with the accumulation of microsomal TG but a reduction in TG in other subcellular compartments.

Expression of adipose differentiation-related protein (ADRP) is conjointly regulated by PU.1 and AP-1 in macrophages.

ADRP is associated with intracellular lipid droplets. We demonstrate the regulatory mechanism for ADRP expression in RAW264.7 macrophages. The ADRP mRNA expression was stimulated by PMA, and synergistically enhanced in association with its protein level in the presence of lipids. A proteasome inhibitor protected the protein from degradation under the lipid-free conditions. One of the possible sites of the PMA action was proved to be an Ets/AP-1 element in the promoter, since mutations of this site reduced the PMA-induced promoter activity, and ligation of this element led to a significant increase in the PMA-responsiveness of homologous or heterologous promoters. Mutations of this site diminished the synergistic effect on the promoter activity induced by PMA and oleic acid, suggesting a possible interaction between this site and the downstream PPARdelta site. EMSA revealed that PU.1 and AP-1 conjointly bound to this site. The juxtaposition of the two sequences was requisite for full activity, since spacer sequences between them decreased the PMA-induced activity. PI3 kinase inhibitor was found to reduce the PMA-induced mRNA expression and promoter activity in parallel with PU.1/AP-1 complex formation on EMSA. From these results, we concluded that the Ets/AP-1 site is an important cis-acting element that regulates the ADRP gene expression in macrophages.

Successful treatment of pure red cell aplasia and autoimmune cytopenia with cyclosporine and prednisolone in a patient with Sjögren's syndrome.

Abstract A 68-year-old woman was admitted to our hospital with xerophthalmia, xerostomia, leukopenia, and thrombocytopenia. She was diagnosed to have Sjögren's syndrome and autoimmune cytopenia. After 11 months, she was readmitted with severe anemia and reticulocytopenia. Mild hemolysis was seen, and bone marrow aspirate showed markedly decreased erythropoiesis. An association of pure red cell aplasia (PRCA) and autoimmune hemolytic anemia was diagnosed. After treatment with cyclosporine and prednisolone, her anemia dramatically improved. We discuss the mechanism of PRCA associated with Sjögren's syndrome.

ADRP stimulates lipid accumulation and lipid droplet formation in murine fibroblasts.

Adipose differentiation-related protein (ADRP) is a lipid droplet-associated protein that is expressed early during adipose differentiation. The present study was undertaken to reveal the role of ADRP in adipose differentiation. In murine fibroblasts infected with green fluorescent protein (GFP)-ADRP fusion protein expression adenovirus vector, confocal microscopic analysis showed the number and size of lipid droplets apparently increased comparing with those of control cells. Overexpressed GFP-ADRP were mainly located at the surface of lipid droplets and appeared to be "ring-shaped." Triacylglycerol content was also significantly (P < 0.001) increased in GFP-ADRP-overexpressed cells compared with control cells. ADRP-induced lipid accumulation did not depend on adipocyte-specific gene induction, such as peroxisome proliferator-activated receptor-gamma, lipoprotein lipase, or other lipogenic genes, including acyl-CoA synthetase, fatty acid-binding protein, and fatty acid transporter. In conclusion, ADRP stimulated lipid accumulation and lipid droplet formation without induction of other adipocyte-specific genes or other lipogenic genes in murine fibroblasts. The detailed molecular mechanisms of ADRP on lipid accumulation remain to be elucidated.