Carotid artery calcification and atherosclerosis at the initiation of hemodialysis in patients with end-stage renal disease.

AIMS: Vascular calcification and atherosclerosis frequently develop in end-stage renal disease (ESRD). Although several reports have investigated both carotid artery calcification (CAAC) and carotid atherosclerosis in ESRD patients, the relationship between the two vascular conditions has remained unclear. The aim of this study was to assess the prevalence of CAAC and carotid artery plaque (CAP) in patients with ESRD and to investigate potential factors contributing to the development of CAAC and CAP. MATERIAL AND METHOD: This cross-sectional study assessed CAAC and CAP using multidetector computed tomography and high-resolution B-mode ultrasonography, respectively, in 135 patients with ESRD at the start of hemodialysis. The prevalence of CAAC and CAP was examined. The risk factors associated with CAAC and CAP were also evaluated using a logistic regression model. RESULTS: CAAC and CAP were found in 71% and 65%, of the patients, respectively. A logistic regression analysis adjusted for age and gender showed that CAAC was significantly associated with age, hypertension, dyslipidemia, serum albumin, calcium-phosphorus product, proteinuria and CAP. In contrast, in the same analysis, CAP was significantly correlated with age, male gender, diabetes, intact parathyroid hormone, proteinuria and CAAC. In the multivariate analysis, CAAC was independently associated with age, hypertension, and calcium-phosphorus product. Male gender was identified as an independent determinant for CAP. Furthermore, CAP remained as an independent risk factor of CAAC (odds ratio (OR): 13.89; 95% confidence interval (CI): 4.08-47.29), and CAAC also showed a high OR for having CAP (OR: 11.74; 95% CI: 4.12-33.51). CONCLUSION: Both CAAC and CAP were associated with traditional and/or non-traditional risk factors. The risk factors of CAAC were different from those of CAP. CAAC or CAP was identified to be an independent risk factor for each other with a high OR, thus suggesting a strong relationship between carotid calcification and atherosclerosis.

Development of Duodenal Ulcers due to the Discontinuation of Proton Pump Inhibitors After the Induction of Sofosbuvir Plus Ledipasvir Therapy: A Report of Two Cases.

Sofosbuvir plus ledipasvir (SOF-LDV) combination therapy is a promising therapy for post-transplant hepatitis C virus (HCV) reinfection. It is known that gastric pH elevation induces lower absorption of ledipasvir; therefore, the use of proton pump inhibitors (PPIs) should be considered regarding dose reduction after SOF-LDV therapy induction. Here, we report two patients who developed duodenal ulcers due to the discontinuation of PPIs after the induction of SOF-LDV therapy for post-transplant HCV reinfection. The first patient was a 71-year-old man who had undergone living donor liver transplantation due to HCV-related liver cirrhosis. Lansoprazole, 30 mg daily, was discontinued upon SOF-LDV therapy induction. Seven days after SOF-LDV therapy induction, gastrointestinal endoscopy revealed the presence of a duodenal ulcer. The second patient was a 54-year-old man who had undergone living donor liver transplantation due to HCV-related end-stage liver disease. Similar to the first patient, rabeprazole sodium was discontinued upon the induction of SOF-LDV therapy. Eighteen days after SOF-LDV therapy induction, gastrointestinal endoscopy revealed the presence of a duodenal ulcer. In both cases, these duodenal ulcers improved after the resumption of the administration of PPIs, and a sustained virologic response at 12 weeks was achieved by SOF-LDV therapy with PPI use. Thus, PPI use should be continued consistently during SOF-LDV therapy for post-transplant HCV reinfection.

Human serum paraoxonase concentration predicts cardiovascular mortality in hemodialysis patients.

AIMS: Human serum paraoxonase (PON1) is associated with high-density lipoprotein, and inhibits oxidative modification of low-density lipoprotein. Therefore, PON1 is supposed to contribute to the prevention of atherosclerosis. We and other investigators have shown that the enzymatic activities and concentrations of PON1 were decreased in maintenance hemodialysis (HD) patients. However, the effect of PON1 status on the long-term outcome of HD patients has not been reported. In this study, we examined the association between baseline PON 1 status and cardiovascular mortality in an observation study of an outpatient HD population. PATIENTS AND METHODS: The relation between baseline cardiovascular risk factors and clinical events was investigated, during 6 years of follow-up, in 81 HD patients (50 males and 31 females) whose enzymatic activities, concentrations and genetic polymorphisms of PON1 had been determined in a previous study. RESULTS: During follow-up for 6 years, we recorded 42 deaths, including 24 fatal cardiovascular events. In univariate analyses, baseline PON1 concentration was associated with not only cardiovascular mortality (p < 0.005), but also all-cause mortality (p < 0.001) during the period of follow-up, as were age, preexisting cardiovascular disease (CVD) and hemoglobin concentration. In a multivariate Cox regression analysis, PON1 concentration retained significant associations with cardiovascular mortality (p < 0.05) and all-cause mortality (p < 0.005) even after correction of known risk factors for CVD or mortality in HD patients. Using Kaplan-Meier survival curves, we assessed the association between low and high concentrations of PON1 divided according to the median value (7.52 U/ml). Significantly increased cardiovascular mortality (log rank 6.125, p = 0.01) and all-cause mortality (log rank 7.113, p < 0.01) were detected in the patients with low PON1 concentrations. CONCLUSIONS: These data suggest that low PON 1 concentration may be an independent predictor of cardiovascular mortality in maintenance HD patients.

Strong green emission from alpha-SiAlON activated by divalent ytterbium under blue light irradiation.

This contribution reports on luminescence properties of divalent ytterbium in alpha-SiAlON at room temperature. Ytterbium-doped alpha-SiAlON powders, with the compositions of (M(1-2x/v)Yb(x))(m/v)Si(12-m-n)Al(m+n)O(n)N(16-n) (M = Ca, Li, Mg, and Y, v is the valency of M, 0.002 < or = x < or = 0.10, 0.5 < or = m = 2n < or = 3.5), were synthesized by sintering at 1700 degrees C for 2 h under 0.5 MPa N2. A single, intense, broad emission band, centered at 549 nm, is observed due to the electronic transitions from the excited state 4f(13)5d to the ground state 4f14 of Yb2+. The luminescence of Yb2+ in alpha-SiAlON occurs at relatively low energy, which is attributable to the large crystal field splitting and nephelauxetic effect due to the nitrogen-rich coordination of Yb2+. The dependence of luminescence properties on the Yb2+ concentration, chemical composition, and annealing is discussed. It is suggested that this novel green phosphor could be applied in white light-emitting diodes (LEDs) when combined with a red phosphor and a blue LED.

Relationship of low-density lipoprotein particle size to plasma lipoproteins, obesity, and insulin resistance in Japanese men.

OBJECTIVE: To determine the clinical characteristics of patients with small low-density lipoprotein (LDL) particles among Japanese men with mild glucose intolerance and to investigate the relationship of LDL particle size to the levels of other plasma lipoproteins, obesity, insulin resistance, and blood pressure (BP). RESEARCH DESIGN AND METHODS: The subjects were 40 men with impaired glucose tolerance or diabetes treated by diet alone, and 40 healthy men matched for age and body mass index (BMI) were used as control subjects. LDL particle size was measured using gradient gel electrophoresis. RESULTS: Of the 40 patients with glucose intolerance, 19 had small LDL (particle size < 25.5 nm) compared with only 4 of the 40 control subjects. In the patients with small LDL, the plasma levels of cholesterol, triglycerides, and apolipoprotein B, the fasting serum immunoreactive insulin, and the waist-to-hip ratio were all higher than in the patients with normal LDL (particle size > or = 25.5 nm), while the high-density lipoprotein cholesterol level was lower. However, there were no significant differences in BMI, BP, or insulin sensitivity in a euglycemic clamp study between the small-LDL and normal-LDL subgroups. CONCLUSIONS: Japanese men with glucose intolerance frequently have small LDL, and this abnormality is associated with other dyslipoproteinemias and increased waist-to-hip ratio.

Decreased expression of a member of the Rho GTPase family, Cdc42Hs, in cells from Tangier disease - the small G protein may play a role in cholesterol efflux.

Cholesterol efflux (CE) is the initial and important step of reverse cholesterol transport (RCT), a major protective system against atherosclerosis. However, most of the molecular mechanism for CE still remains to be clarified. In the present study, cDNA subtraction revealed that the expression of a member of the Rho GTPase family, Cdc42Hs, was markedly decreased in both passaged fibroblasts and macrophages (Mφ) from patients with Tangier disease (TD), a rare lipoprotein disorder with reduced CE. This small G protein is known to have many cell biological activities such as rearrangement of actin cytoskeleton and vesicular transport, however the association between this molecule and lipid transport has never been reported. We demonstrate that MDCK cells expressing the dominant negative form of Cdc42Hs had reduced CE, inversely ones expressing the dominant active form had increased CE. From these observations, we would like to raise a novel hypothesis that this type of small G protein may play a role in some steps of CE. To our knowledge, the present study is the first demonstration that the expression of this molecule is altered in cells from human disease.

Significance of angiotensin I-converting enzyme and angiotensin II type 1 receptor gene polymorphisms as risk factors for coronary heart disease.

The D allele of an insertion/deletion (I/D) polymorphism in the angiotensin I-converting enzyme (ACE) gene is associated with a risk of myocardial infarction, and the relative risk associated with the ACE D allele is increased by the C allele of an angiotensin II type 1 receptor (AT1R) gene polymorphism (an A-->C transversion at nucleotide position 1166) [28]. The relation of the ACE and AT1R gene polymorphisms to coronary heart disease and the severity of coronary artery stenosis has now been investigated in 133 patients with myocardial infarction (MI) or angina pectoris who underwent coronary angiography and in 258 control subjects. The frequency of the ACE DD genotype as compared with non-DD was significantly higher in the patients who experienced an MI and in the low-risk patients than that in the controls (P < 0.05). The DD genotype showed a significantly increased risk of MI (odds ratio 1.85). The frequency of the AT1R A/C genotypes did not differ between the patients and the controls. The severity of coronary stenosis in the patients was estimated by the number of affected vessels (> 75% stenosis) and the coronary score of Gensini. Neither the number of affected vessels nor the coronary score differed among the ACE I/D genotypes. However, the number of affected vessels was significantly greater in patients with the AT1R AC genotype than in those with the 4A genotype (1.93 +/- 0.27 vs. 1.27 +/- 0.99; P < 0.05) (CC genotype was not found in the patients). After excluding patients with diabetes mellitus, the coronary score of those with the AC genotype was also significantly higher than in those with the AA genotype (51.7 +/- 34.4 vs. 18.2 +/- 23.3; P < 0.01). These results suggest that the ACE D allele is associated with the occurrence of myocardial infarction, while the AT1R C allele is involved in the development of the coronary artery stenosis.

A polymorphism upstream from the human paraoxonase (PON1) gene and its association with PON1 expression.

Human serum paraoxonase (PON1) is an esterase that has been shown to decrease the susceptibility of lipoproteins to lipid peroxidation. We found a polymorphism of cytosine/thymidine (-108C/T, the number is from the ATG codon) in the upstream region of the PON1 gene. The luciferase activity was lower in the -108T allele than in the -108C allele. The serum PON1 concentrations in 132 normal subjects were as follows: -108CC>-108CT and>-108TT genotypes. The polymorphism upstream from the PON1 gene is associated with transcription of the PON1 gene and the serum PON1 concentration.

Assessment of damage and recovery of sinusoidal endothelial cell function by in vivo hyaluronic acid uptake in cold-preserved and transplanted rat livers.

We sought to evaluate the significance of endogenous hyaluronic acid levels and in vivo uptake of exogenous hyaluronic acid as markers of liver endothelial cell damage and correlate these findings to graft survival/function in a rat orthotopic liver transplant model. Endogenous hyaluronic acid levels were measured after orthotopic liver transplantation performed with freshly explanted livers, with livers preserved for 30 hr, and after sham operation. Exogenous hyaluronic acid uptake was evaluated in six study groups: fresh liver grafts, livers preserved for 12 hr, 24 hr, 30 hr and 48 hr, and sham-operated livers. Endogenous hyaluronic acid levels fell after orthotopic liver transplantation with freshly harvested livers and after sham operation, but rose in animals transplanted with livers preserved for 30 hr (P<0.01 vs. sham operation). In the preserved group, there was no difference in endogenous hyaluronic acid levels between survivors and nonsurvivors. Uptake of exogenous hyaluronic acid was significantly lower after orthotopic liver transplant with grafts preserved for 12 hr than after sham operation or orthotopic liver transplant with nonpreserved livers (P<0.05). Hyaluronic acid uptake further deteriorated in the 24-, 30-, and 48-hr groups. No significant difference in hyaluronic acid elimination rate was found when results obtained from livers preserved for extended periods (>12 hr) were compared in survivors and nonsurvivors. Hyaluronic acid uptake was reevaluated in surviving animals after 2 weeks. Completely restored function was observed in all survivors, indicating recovery of endothelial cells. We conclude that endogenous hyaluronic acid levels and exogenous hyaluronic acid uptake are reliable markers of liver sinusoidal endothelial cell function and that normal or moderately compromised hyaluronic acid uptake is associated with good graft function. On the other hand, endothelial cell dysfunction suggested by poor hyaluronic acid elimination is not a completely reliable predictor of subsequent deterioration of graft function in rat liver transplantation.

Beneficial effect of thromboxane A2 synthetase inhibitor on cold-stored rat liver.

Prostanoids such as prostacyclin and thromboxane A2 have recently been suggested to play important roles in cold ischemia/reperfusion injury. The purpose of this study was to investigate the effect of thromboxane A2 synthetase inhibitor (OKY-046) on cold-stored livers of the rat using an ex vivo perfusion system. Addition of OKY-046 to preservation solution and the perfusate of livers stored cold (4 degrees C) in lactated Ringer's solution resulted in significantly lower glutamic pyruvic transaminase release (3.01 +/- 0.86 IU/g liver vs. 1.79 +/- 1.08 IU/g liver at 120 min after perfusion; P < 0.05), reduced perfusate ammonia levels (8.51 +/- 2.51 micrograms/dl/g liver vs. 3.62 +/- 1.71 micrograms/dl/g liver at 60 min; P < 0.05 and thereafter), lower perfusate taurocholate levels (0.63 +/- 0.10 vs. 0.18 +/- 0.05 at 15 min; P < 0.01 and thereafter), perfusate hyaluronic acid clearance (0.934 +/- 0.132 vs. 0.76 +/- 0.127 at 30 min; P < 0.05 and thereafter), and a reduced number of trypan blue-positive sinusoidal lining cells (50.1 +/- 9.9%; vs. 17.4 +/- 7.0%; P < 0.01). Histologically, the liver preserved for 6 hr in simple cold lactated Ringer's solution exhibited interstitial edema, various degrees of hepatocyte swelling, and sinusoidal stenosis, as well as dilatation, while the livers treated with OKY-046 demonstrated much less hepatocyte swelling, and change in sinusoidal width was nearly absent. We conclude that OKY-046 reduces post-preservation reoxygenation injury by protecting sinusoidal endothelial cells and hepatocytes.

Immunohistochemical study of lung adenocarcinoma using monoclonal antibody for 60-kilodalton antigen in type II pneumocytes and nonciliated bronchiolar epithelial cells. Comparison with two antisurfactant apoprotein antibodies.

Monoclonal antibody KP16D3 was produced by immunizing mice with monkey bronchoalveolar lavage. KP16D3 revealed the immunohistochemical reactivity in the cytoplasm of some nonciliated bronchiolar epithelial cells and type II pneumocytes and thereby recognized specifically a protein with an apparent molecular weight of 60 kD with the use of Western blotting and immunoaffinity column chromatography followed by SDS-PAGE. Examination of 76 primary and 4 metastatic lung carcinomas in primary lung carcinoma KP16D3 showed immunohistochemical positivity only to mucin-nonproducing papillary adenocarcinoma (27/28) and bronchioloalveolar carcinoma (2/2), except for one case of large cell carcinoma. All other primary lung carcinomas such as squamous cell carcinoma, acinar adenocarcinoma, and small cell carcinoma had negative results. From these findings, KP16D3 seems to be an effective immunohistochemical marker of mucin-nonproducing papillary adenocarcinoma and bronchioloalveolar carcinoma of the lung and it appears to be useful to investigate both the histogenesis and functional expression of primary lung adenocarcinoma.

Ferritin correlates with C-reactive protein and acute phase serum amyloid A in synovial fluid, but not in serum.

OBJECTIVE: To evaluate ferritin concentration in serum and synovial fluid (SF) as a marker of activity of arthritis in comparison with C-reactive protein (CRP) and acute-phase serum amyloid A protein (A-SAA). METHODS: We determined the concentrations of ferritin, CRP and A-SAA in paired serum and SF in 34 rheumatoid arthritis (RA) and 21 osteoarthritis (OA) patients. The erythrocyte sedimentation rate (ESR) was also measured. RESULTS: The serum concentrations of ferritin, CRP and A-SAA were 93 +/- 76 (mean +/- SD) ng/ml, 4 +/- 5 mg/ml, 8 +/- 4 mg/ml in OA and 140 +/- 227, 59 +/- 34, 289 +/- 223 in RA, respectively. There was no significant difference in serum ferritin levels between OA and RA, and serum ferritin did not correlate with ESR, CRP or A-SAA. Both serum CRP and A-SAA levels were significantly higher in RA than in OA (p < 0.0001, p < 0.0001), and correlated with ESR in all arthritis (r = 0.658, p < 0.0001, r = 0.404, p < 0.01), respectively. Serum CRP levels correlated with A-SAA levels in serum (r = 0.727, p < 0.0001). In SF, the concentrations of ferritin, CRP and A-SAA in RA (421 +/- 307, 25 +/- 20 and 39 +/- 41) were significantly higher (p < 0.01, p < 0.0001, p < 0.001) than those in OA (202 +/- 220, 2 +/- 2 and 2 +/- 2), respectively. There were significant correlations among SF ferritin, CRP and A-SAA. CONCLUSION: Ferritin levels in SF but not in serum are significantly elevated in RA more than in OA, and ferritin correlated with CRP or A-SAA in SF, but not in serum. Higher levels of SF ferritin, as well as SF CRP and SF A-SAA, seem to reflect greater degrees of joints inflammation in RA and OA.

Des-gamma-carboxy prothrombin and proliferative activity of hepatocellular carcinoma.

BACKGROUND: Des-gamma-carboxy prothrombin (DCP) is a useful marker for the prognosis of hepatocellular carcinoma (HCC). In this report we investigated the relationship between the positivity of DCP and proliferative activity of HCC and discuss the cause of poor prognosis of DCP-positive HCC. METHODS: Immunohistochemical and clinicopathologic study was done in 114 patients with resected HCC measuring less than 6 cm in diameter by using monoclonal antibody for proliferating cell nuclear antigen (PCNA). RESULTS: PCNA labeling index (PCNA-LI) was significantly higher in the patients with DCP-positive HCC than in those with DCP-negative HCC; also a positive correlation was noted between the PCNA-LI and the DCP level. We divided patients into two groups according to the PCNA-LI. In the high PCNA-LI group the patients with DCP-positive HCC exhibited a higher PCNA-LI than did the patients with DCP-negative HCC. As for pathologic prognostic factors, the DCP-positive high PCNA-LI group showed the highest incidence of tumor thrombus of the portal vein and intrahepatic metastasis while also exhibiting the lowest recurrence-freedom rate. From multivariate analysis we find that DCP, as well as PCNA-LI, is one of the risk factors for recurrence of HCC after hepatectomy. CONCLUSIONS: Our results thus suggest that DCP-positive HCC showed high PCNA-LI, and this might be the main cause for early intrahepatic spread and poor prognosis of DCP-positive HCC.

Partial hepatic grafting: porcine study on critical volume reduction.

BACKGROUND: The safe limit of volume reduction in partial hepatic transplantation, including extracorporeal hepatic resection, remains to be clarified. This study evaluated such a limit and pathologic features associated with transplantation of a less than critical volume. METHODS: Partial hepatic grafting was performed in a porcine orthotopic autotransplantation model. According to the remnant liver volume, animals were classified into three groups: group 1, 73.8% +/- 4.2% (SD); group 2, 52.6% +/- 6.7%; and group 3, 29.4% +/- 6.7% of the whole liver (n = 5 each). RESULTS: Three-day survival was achieved in five (100%), four (80%), and zero animals, respectively. All animals in group 3 died of graft nonfunction; their intraoperative clearance of the total bile acids was significantly worse than the other groups (p < 0.01). After operation the clearance of the total bile acids and hyaluronic acid, which is selectively cleared by hepatic endothelial cells, was significantly better in group 1 than group 2 (p < 0.01 and < 0.05, respectively). On histologic examination postperfusion biopsy specimens of group 3 exhibited severe ischemic changes and portosinusoidal hyperemia, whereas that of groups 1 and 2 exhibited only mild ischemic damages. CONCLUSIONS: Transplantation of less than 30% of expected full liver volume could lead to primary graft nonfunction after partial hepatic grafting.

Suppression of plasma cholesteryl ester transfer protein activity in acute hyperinsulinemia and effect of plasma nonesterified fatty acid.

Cholesteryl ester transfer protein (CETP) is a major determinant of the plasma high-density lipoprotein cholesterol (HDL-C) level and plays an important role in the reverse cholesterol transport system. The purpose of this study was to determine the effect of acute hyperinsulinemia on plasma CETP activity in normal subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). Hyperinsulinemia was achieved using the hyperinsulinemic-euglycemic clamp. CETP activity was determined as the transfer of radiolabeled cholesterol in HDL3 to acceptor lipoprotein. Mean plasma CETP activity during an insulin infusion in both subject groups was significantly decreased compared with the mean basal activity. Suppression of plasma CETP activity in the NIDDM patients was significantly less than in the normal subjects (-4.2% +/- 7.9% v -9.6% +/- 6.4%, P < .02). Regression analysis showed that this suppression was correlated with plasma nonesterified fatty acid (NEFA) levels after the clamp and with the magnitude of the NEFA decrease (r = .318, P < .02 and r = .292, P < .05, respectively). The data suggest that acute hyperinsulinemia reduces plasma CETP activity through a decrease in plasma NEFA.

Serum arylesterase/diazoxonase activity and genetic polymorphisms in patients with type 2 diabetes.

Human serum paraoxonase (PON1) is associated with high-density lipoprotein (HDL) and inhibits the oxidation of low-density lipoprotein (LDL) in vitro, suggesting that PON1 protects against atherosclerosis. We detected 3 polymorphisms of the PON1 gene and investigated PON1 enzyme activities as paraoxonase (PON), arylesterase (ARYL) and diazoxonase (DIAZ), and serum PON1 concentration in 106 patients with type 2 diabetes and 161 control subjects. All 3 enzyme activities and specific activities of PON1 in diabetic patients were significantly lower than those in controls, while there was no difference in serum PON1 concentration between the patient and control groups. The specific activities of PON, ARYL, and DIAZ in patients were 6.82 +/- 3.14 nmol x min(-1) x U(-1) (mean +/- SD, U; unit for serum PON1 concentration), 4.77 +/- 0.17 micromol x min(-1) x U(-1), and 193 +/- 92 nmol x min(-1) x U(-1), respectively, whereas those in controls were 9.33 +/- 3.92 nmol x min(-1) x U(-1), 5.36 +/- 0.14 micromol x min(-1) x U(-1), and 242 +/- 103 nmol x min(-1) x U(-1), respectively. There was no significant difference in the allelic frequencies of -108C/T, 55L/M, or 192Q/R between the patient and control groups. When each enzyme activity was compared between the patient and control groups in each genotype subgroup, all activities were lower in the patient group. The PON and ARYL activities were lower in patients with retinopathy or nephropathy than in those without such complications, and the ARYL activity was also lower in patients with neuropathy. In conclusion, all specific enzyme activities of PON1 were lower in patients with type 2 diabetes independent of the -108C/T, 55L/M, or 192Q/R polymorphism, and this impaired PON1 function may be involved in development of diabetic microangiopathy.

Screening for variants of the uncoupling protein 2 gene in Japanese patients with non-insulin-dependent diabetes mellitus.

We examined genetic mutations in the coding regions of the uncoupling protein 2 (UCP2) gene in 100 patients with non-insulin-dependent diabetes mellitus (NIDDM). The sequences of each exon-intron boundary were detected by polymerase chain reaction (PCR) using specific primer pairs designed in the cDNA sequence of UCP2 and a cycle-sequence method. Using the specific primer pairs in the intron 5'- or 3'-untranslated region, each exon with its exon-intron boundaries was amplified with the PCR method, and the PCR products were analyzed using a single-strand conformation polymorphism (SSCP) method. One nucleotide substitution in exon 4 was found, which exchanged Ala (gcc) at position 55 of the amino acid sequence for Val (gtc), previously reported in Denmark by Urhammer et al in 1997. The polymorphism was reanalyzed in all patients and 120 normal subjects using a PCR-restriction fragment length polymorphism method. There was no difference in the genotype distribution between patients and normal subjects, and our genotype distribution was similar to the Danish study. Furthermore, there were no clinical differences between genotype groups among the patients. No other mutation including the exon-intron boundary was found in these patients. Genetic mutations of UCP2 may not be commonly associated with obesity or diabetes in Japanese subjects.

Serum paraoxonase activity and its relationship to diabetic complications in patients with non-insulin-dependent diabetes mellitus.

Paraoxonase (PON) is an esterase associated with high-density lipoprotein (HDL). Serum PON activity is affected by PON gene polymorphism (L/M, Leu-Met54, and Q/R, Gln-Arg191). We investigated PON activity and polymorphism in 108 patients (53 men and 55 women) with non-insulin-dependent diabetes mellitus (NIDDM) and 161 control subjects (82 men and 79 women) matched to the patients by age and gender. Serum PON activity was determined using paraoxon as a substrate. PON gene polymorphisms were detected by the restriction fragment length polymorphism method after a polymerase chain reaction. The mean PON activity in the patients was significantly lower than in the controls (116+/-55 and 162+/-57 U/L, respectively, P < .001). The distribution of each genotype showed no difference between the patient and control groups, and PON activity increased in the order of the QQ < OR < RR genotype and MM < LM < LL genotype in both groups. However, among each genotype subgroup, the activity was lower in patients than in controls. Forty-one patients with retinopathy had lower PON activity than those without the complication (94+/-36 and 129+/-61 U/L, respectively, P < .002). There was also a significant difference in PON activity between patients with and without overt proteinuria (93+/-38 and 122+/-58 U/L, respectively, P < .05). Logistic analysis showed that serum PON activity was one of the significant factors for retinopathy. These results suggest that decreased PON activity in patients with NIDDM is involved in diabetic vascular complications.

Effect of diabetes mellitus on hepatic resection.

We evaluated the effect of diabetes mellitus on mortality and morbidity after elective hepatic resections. Of 209 patients who underwent hepatic resections between April 1985 and July 1990, 49 (23.4%) were diabetic. Postoperative morbidity was more common among diabetics than among nondiabetics (75.5% vs 51.3%), mainly due to hepatic decompensation (55.1% vs 36.3%) and intraperitoneal sepsis (18.4% vs 6.3%). However, their incidence of hospital death (2% vs 2.5%), mean +/- SD postoperative hospital stay (36.1 +/- 20.2 days vs 29.4 +/- 28.2 days), and long-term survival were comparable with those of nondiabetics. Diabetics with and without complications were similar in preoperative or postoperative insulin requirement, duration of diabetes, and preoperative fasting glucose. Nevertheless, all eight patients with 24-hour urinary glucose excretion above 1 g developed complications. We conclude that diabetics are at a high risk of morbidity, but not of mortality after elective hepatic resection.

Platelet volume and urinary prostanoid metabolites in non-insulin-dependent diabetes mellitus.

To evaluate platelet activity in patients with non-insulin-dependent diabetes mellitus (NIDDM), we measured the mean platelet volume (MPV) and 24-hour urinary excretion of 11-dehydro-thromboxane B2 (11-dTXB2) and 6-keto-prostaglandin F1 alpha (6-kPGF1 alpha), stable metabolites of thromboxane A2 and prostacyclin, respectively. The MPV of the 103 subjects in the NIDDM group were 10.72 +/- 0.82 fl for males and 10.52 +/- 1.01 fl for females (mean +/- SD), significantly higher than those of normal controls (9.95 +/- 0.75 fl for males and 9.84 +/- 0.72 fl for females). The MPV of patients with NIDDM showed positive correlations with fasting plasma glucose level and HbA1c (r = 0.234, P < 0.05; r = 0.267, P < 0.01, respectively). The urinary excretion of 11-dTXB2 was greater in the NIDDM group (7.58 +/- 4.42 micrograms/day for males and 5.65 +/- 2.38 micrograms/day for females) than in the normal controls (4.61 +/- 2.31 and 3.83 +/- 1.60, respectively), suggesting that the synthesis of thromboxane A2 by platelets may be accelerated in vivo in patients with NIDDM. The urinary 6-kPGF1 alpha was not different between the NIDDM group and normal controls among the males, but was greater in the NIDDM group among the females. As MPV showed a positive correlation (r = 0.364, P < 0.05) with urinary excretion of 11-dTXB2, MPV may be related to platelet activity. These findings suggest that the platelets of patients with NIDDM may be in a hyperactive state.