Explore the vast range of titles available.

Prevalence and Clinicopathological Characteristics of Islet Amyloid in Chinese Patients With Type 2 Diabetes Hai-Lu Zhao 1 , Fernand M.M. Lai 2 , Peter C.Y. Tong 1 , Ding-Rong Zhong 3 , Di Yang 4 , Brian Tomlinson 1 and Juliana C.N. Chan 1 1 Department of Medicine and Therapeutics, The Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong SAR, China 2 Department of Anatomical and Cellular Pathology, The Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong SAR, China 3 Department of Pathology, Chinese PLA General Hospital, Beijing, China 4 Department of Pathology, Peking Union College Hospital, Beijing, China Address correspondence and reprint requests to Hai-Lu Zhao, MD, Department of Medicine and Therapeutics, The Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, N.T., Hong Kong. E-mail: zhaohailu{at}cuhk.edu.hk Abstract Islet amyloid has been suggested to be an important link between insulin resistance and β-cell dysfunction in type 2 diabetes. To investigate the prevalence and clinicopathological characteristics of islet amyloid, we examined consecutive autopsies of 235 Chinese patients with type 2 diabetes and 533 nondiabetic subjects. Islet amyloid deposits were identified using Congo red staining and quantitated by image analysis. We found that 3.0% of the nondiabetic subjects versus 39.6% of the diabetic patients displayed islet amyloid ( P < 0.001). In diabetic patients, the amyloid deposits occupied a mean islet area of 36.2%, which was positively associated with BMI, blood pressure, and glycemic control. Pancreatic fibrosis and fat infiltration were more frequently found in diabetic patients with islet amyloid than those without islet amyloid, whereas pancreatic arteriosclerosis was identified in all diabetic patients. These findings suggest that islet amyloid deposits reflect greater insulin resistance and islet failure in a subgroup of type 2 diabetic patients. Islet failure may also have been exacerbated by fat infiltration, fibrosis, and arteriosclerosis. Optimal blood pressure and metabolic control may reduce these pathological changes and help preserve islet cell mass.  H-E, hematoxylin-eosin IAPP, islet amyloid polypeptide PAS, periodic acid Schiff Footnotes Accepted July 30, 2003. Received March 18, 2003. DIABETES

MicroRNAs (miRNAs) are noncoding, single-stranded RNA molecules that have important roles in a number of physiological and pathological processes. Previous studies have proved that miRNAs targeting ZEB1 and ZEB2 may repress epithelial-to-mesenchymal transition. In this work, we studied the intrarenal expression of miR-200 family, miR-205 and miR-192 in patients with immunoglobulin A (IgA) nephropathy. We studied 43 patients with biopsy-proven IgA nephropathy (IgA group). The intrarenal expression of miRNAs was quantified and compared with that of 15 patients with noninflammatory glomerulosclerosis (GS group) and 20 patients with nephrectomy for kidney cancer as controls (CTL group). The level of intrarenal miR-200c was downregulated, whereas the levels of intrarenal miR-141, miR-205 and miR-192 were upregulated in IgA but not GS group. Proteinuria significantly correlated with the intrarenal expression of miR-200c (r=−0.324, P=0.011) and glomerular filtration rate (GFR) significantly correlated with the intrarenal expression of miR-205 (r=−0.280, P=0.030). The degree of tubulointerstitial scarring correlated with miR-205 expression (r=0.389, P=0.021), whereas glomerulosclerosis correlated with miR-192 expression (r=−0.311, P=0.045). The rate of GFR decline significantly correlated with the intrarenal expression of miR-192 (r=0.373, P=0.015). The intrarenal expression of E-cadherin significantly correlated with the intrarenal expression of miR-200c (r=0.392, P=0.002). The results show that intrarenal expression of miR-200c, miR-141, miR-205 and miR-192 was diversely regulated and correlated with disease severity and progression in patients with IgA nephropathy. These miRNA species may be important in the pathogenesis and progression of IgA nephropathy.

Association of Glomerulopathy With the 5′-End Polymorphism of the Aldose Reductase Gene and Renal Insufficiency in Type 2 Diabetic Patients Hai-Lu Zhao 1 , Peter C.Y. Tong 1 , Fernand M.M. Lai 2 , Brian Tomlinson 1 and Juliana C.N. Chan 1 1 Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong SAR, China 2 Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong SAR, China Address correspondence and reprint requests to Hai-Lu Zhao, MD, PhD, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong. E-mail: zhaohailu{at}cuhk.edu.hk Abstract The expression of nephropathy in type 2 diabetes has several levels of abnormalities. To define the primary abnormalities of diabetic nephropathy, we conducted an autopsy study of 186 consecutive patients with type 2 diabetes to determine correlations among the aldose reductase gene, renal histopathologies, extracellular matrix, glomerular function, and clinical characteristics. Compared with cases of near-normal renal structure ( n = 51) and atypical diabetic glomerulopathy ( n = 75), patients with classic diabetic glomerulopathy ( n = 60) had advanced glomerular disease, as reflected by elevated plasma creatinine levels (133.2 ± 59.8 vs. 166.0 ± 65.7 vs. 243.8 ± 82.6 μmol/l; P < 0.001), glomerular matrix fractions (20.8 ± 6.7 vs. 33.5 ± 16.8 vs. 39.2 ± 14.3%; P < 0.001), and risk of renal failure (odds ratio [OR] 1 vs. 3.5 vs. 21.4; P < 0.001). Compared with noncarriers of the aldose reductase z-2 allele ( n = 92) and z-2 heterozygotes ( n = 77), z-2 homozygotes ( n = 17) had elevated plasma creatinine (164.1 ± 73.7 vs. 190.6 ± 60.9 vs. 241.1 ± 86.2 μmol/l; P < 0.001) and an increased risk of classic diabetic glomerulopathy (OR 1 vs. 0.9 vs. 3.3; P = 0.026). Overexpression of transforming growth factor-β1, mesangial cell transdifferentiation by expression of α-smooth muscle actin, and aberrant deposition of collagen type IV, fibronectin, and laminin were found in classic diabetic glomerulopathy. These data suggest genetic, biochemical, pathophysiological, and clinical correlations among the aldose reductase gene, extracellular matrix, classic diabetic glomerulopathy, and renal insufficiency. Gene mutation, cellular transdifferentiation, growth factor upregulation, extracellular matrix expansion, and glomerular filtration impairment are the primary abnormalities in type 2 diabetic patients with nephropathy. ESRD, end-stage renal disease GFR, glomerular filtration rate MDRD, Modification of Diet in Renal Disease PAS, periodic acid Schiff α-SMA, α-smooth muscle actin TGF-β1, transforming growth factor-β1 Footnotes Accepted August 9, 2004. Received May 13, 2004. DIABETES

Dyslipidemia complicates renal function leading to disturbances of major homeostatic organs in the body. Here we examined the effect of chronic renal dysfunction induced by uninephrectomy on fat redistribution and lipid peroxidation in rats treated with an angiotensin-converting enzyme (ACE) inhibitor (lisinopril) for up to 10 months. Uninephrectomized rats developed fat redistribution and hypercholesterolemia typical of chronic renal failure when compared with sham-operated rats or lisinopril-treated uninephrectomized rats. The weight of the peri-renal fat was significantly less in the untreated compared to the lisinopril-treated uninephrectomized rats or those rats with a sham operation. We also found that there was a shift of heat-protecting unilocular adipocytes to heat-producing multilocular fat cells in the untreated uninephrectomized rats. Similarly in these rats we found a shift of subcutaneous and visceral fat to ectopic fat with excessive lipid accumulation and lipofuscin pigmentation. Lisinopril treatment prevented fat redistribution or transformation and lipid peroxidation. This study shows that ACE inhibition may prevent the fat anomalies associated with chronic renal dysfunction.

We report a patient with chronic diabetes and was referred for recent onset proteinuria. Light microscopy of the renal biopsy specimen showed mildly expanded mesangium with mesangial hypercellularity and segmental sclerosis, features compatible with diabetic glomerulosclerosis. However, crystalglobulin-induced nephropathy with crystal deposit was identified on electron microscopy. Renal biopsy is often performed for diabetic patients who present with proteinuria and light microscopy often shows features of diabetic glomerulosclerosis. Additional information may occasionally be revealed on electron microscopy, altering the subsequent plan of management.

In skeletal muscle cells, insulin stimulates cytoskeleton actin remodeling to facilitate the translocation of glucose transporter GLUT4 to plasma membrane. Defect of insulin-induced GLUT4 translocation and actin remodeling may cause insulin resistance. Free fatty acids cause insulin resistance in skeletal muscle. The aim of this study was to investigate the effects of fatty acids on glucose transport and actin remodeling. Differentiated L6 muscle cells expressing c-myc epitope-tagged GLUT4 were treated with palmitic acid, linoleic acid and oleic acid. Surface GLUT4 and 2-deoxyglucose uptake were measured in parallel with the morphological imaging of actin remodeling and GLUT4 immunoreactivity with fluorescence, confocal and transmission electron microscopy. Differentiated L6 cells showed concentration responses of insulin-induced actin remodeling and glucose uptake. The ultrastructure of insulin-induced actin remodeling was cell projections clustered with actin and GLUT4. Acute and chronic treatment with the 3 fatty acids had no effect on insulin-induced actin remodeling and GLUT4 immunoreactivity. However, insulin-mediated glucose uptake significantly decreased by palmitic acid (25, 50, 75, 100 μmol/L), oleic acid (180, 300 μmol/L) and linoleic acid (120, 180, 300 μmol/L). Oleic acid (120, 300 μmol/L) and linoleic acid (300 μmol/L), but not palmitic acid, significantly decreased insulin-mediated GLUT4 translocation. These data suggest that fatty acids inhibit insulin-induced glucose transport associated with actin remodeling in L6 muscle cells.

To evaluate the applicability of the University of California Los Angeles Integrated Staging System (UISS) in predicting the prognosis of Chinese patients with localized renal cell carcinoma after radical nephrectomy, with reference to that reported by Patard et al in an international multicenter study (J Clin Oncol 2004, 22:3316-3322). One hundred and twenty-eight Chinese patients with localized renal cell carcinoma were stratified into low risk (LR), intermediate risk (IR) and high risk (HR) groups according to the UISS, based on the TMN staging and Fuhrman grading of the tumor and the Eastern Cooperative Oncology Group performance status of the patients. The survival curves of each risk group were then calculated. The number of patients in the LR, IR and HR was 24 (18.8%), 94 (73.4%) and 10 (7.8%) respectively. The estimated 2-year survival rates were 100%, 89.9% and 100% for the LR, IR and HR groups respectively. Whereas the estimated 5-year survival rates were 93.3%, 72.4% and 80% for the LR, IR and HR groups respectively. The LR and IR patients had comparable 2-year and 5-year estimated survival rates with those reported by Patard et al. However, the estimated survival rate for HR patients was better than that reported. UISS provided a valuable tool in predicting the survival of Chinese patients with localized renal cell carcinoma of LR and IR groups, as reported in other international centers. Further large scale study may be needed to confirm the applicability in HR population.