We aimed to clarify the usefulness of measuring the flow mediated dilatation (FMD) in patients with type 2 diabetes mellitus without and with coronary heart disease (CHD). The FMD was measured in 480 ...patients with type 2 diabetes and in 240 nondiabetic subjects. The FMD was significantly lower in the subjects with CHD (n = 145, 5.4±3.2%) than in those without CHD (n = 95, 6.9±3.5%) among the nondiabetic subjects. The FMD was also lower in the subjects both with CHD (n = 161, 5.6±2.8%) and without CHD (n = 319, 6.1±3.3%) among the patients with diabetes compared to those without both diabetes and CHD. The FMD showed a significant positive correlation with the estimated glomerular filtration rate (eGFR) in the diabetic patients without CHD, while there was no significant association in those with CHD. The FMD was significantly lower with the progressive stages of the GFR or albuminuria in the patients without CHD among those with diabetes, although the FMD was not different in those with CHD. In conclusion, the FMD is considered to be useful for the detection of atherosclerosis in patients with type 2 diabetes, even if overt macroangiopathy is not diagnosed.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The relationship between hypoglycemia and the dose of insulin used in patients with type 2 diabetes mellitus was investigated by continuous glucose monitoring (CGM).
In total, 83 CGM studies were ...performed in 70 outpatients with type 2 diabetes receiving treatment by subcutaneous insulin injection.
The total dose of insulin, bolus insulin dose, and basal insulin dose used in the subjects were 32±18 units, 19±13 units, and 13±8 units, respectively. The proportion of time in the hypoglycemic range (blood glucose<3.9 mmol/L) during CGM was positively correlated with the bolus insulin ratio (bolus/total insulin dose, r=0.22, P=0.04), although it was not associated with the total dose of insulin or the hemoglobin A1c (HbA1c) level. It was negatively correlated with the mean blood glucose (r=-0.38, P<0.01), whereas it was not associated with the SD or the mean amplitude of glycemic excursions (MAGE). The proportion of time in the hypoglycemic range was significantly greater in the subjects with a bolus insulin ratio of ≥0.6 (3.2±4.4%, n=42) than a ratio of <0.6 (1.2±3.0%, n=41), although the HbA1c level, total dose of insulin, mean blood glucose, SD, and MAGE were not significantly different between the two groups.
An excessive dose of bolus insulin might increase the duration of hypoglycemia, independently from the HbA1c levels, in patients with type 2 diabetes mellitus receiving subcutaneous insulin injection.
We aimed to study the association between urinary liver-type fatty acid-binding protein (L-FABP), a biomarker of tubulointerstitial injury, and the clinical characteristics of normoalbuminuric and ...albuminuric patients with type 2 diabetes in order to detect the factors affecting urinary L-FABP.
Urinary L-FABP levels were measured in 788 patients with type 2 diabetes and again in 666 patients at 6 months after the initial measurement. The association between the urinary L-FABP level and the clinical parameters was investigated in a retrospective cross-sectional study and a subsequent observation.
The HbA1c (odds ratio (OR): 1.42; 95% confidence interval (CI): 1.11 - 1.79; P < 0.01), systolic blood pressure (OR: 1.03; 95% CI: 1.01 - 1.05; P < 0.01) levels and estimated glomerular filtration rate (OR: 0.98; 95% CI: 0.96 - 1.00; P = 0.01) were significantly associated with the high levels of urinary L-FABP (> 8.4 μg/gCr) in normoalbuminuric patients. However, a logistic regression analysis revealed that use of renin-angiotensin system (RAS) inhibitors (OR: 2.22; 95% CI: 1.16 - 4.89; P = 0.02), urinary albumin-to-creatinine ratio (ACR) (OR: 1.01; 95% CI: 1.00 - 1.01; P < 0.01) and serum HDL-cholesterol concentration (OR: 0.33; 95% CI: 0.11 - 0.89; P = 0.03) were significantly associated in albuminuric patients. In the follow-up observation, the change in urinary L-FABP was found to be significantly (P < 0.01) influenced by the change in the HbA1c level in both the normoalbuminuric and albuminuric patients.
High urinary L-FABP is associated with part of the current metabolic abnormalities, including high levels of HbA1c and systolic blood pressure among normoalbuminuric patients with type 2 diabetes.
We histopathologically examined Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3)-positive hepatocellular carcinoma (HCC) and protein induced by vitamin K absence (PIVKA) II-positive HCC ...to clarify the efficacy of these markers for predicting a poor prognosis.
Serum AFP-L3 and PIVKA II was measured in 110 HCC patients. AFP-L3 was measured by lectin-affinity electrophoresis coupled with antibody-affinity blotting, and PIVKA II by using a high-sensitivity kit. The growth type, capsule formation, capsule infiltration, portal vein invasion, intrahepatic metastasis and histological tumor grade were evaluated pathologically.
Thirty-eight (35%) HCC patients were AFP-L3-positive, and 63 (57%) were PIVKA II-positive. In AFP-L3-positive HCC, the frequencies of an infiltrative growth type (positive : negative = 66% : 42%, P = 0.027) and a poorly differentiated type (positive : negative = 32% : 6%, P < 0.001) were significantly higher than in AFP-L3-negative HCC. In PIVKA II-positive HCC, the frequencies of an infiltrative growth type (positive : negative = 62% : 28%, P < 0.001), vascular invasion (positive : negative = 63% : 26%, P < 0.001), and intrahepatic metastasis (positive : negative = 38% : 4%, P < 0.001) were significantly higher than in PIVKA II-negative HCC. In both AFP-L3- and PIVKA II-positive HCC, the frequency of a poorly differentiated growth type was significantly higher than in HCC positive for either AFP-L3 or PIVKA II or HCC negative for both AFP-L3 and PIVKA II (both positive : either positive : both negative = 37% : 12% : 0%; P = 0.014, P < 0.001, respectively).
AFP-L3 was related to progression from moderately differentiated to poorly differentiated HCC, whereas PIVKA II was more specific to vascular invasion. PIVKA II is therefore likely to be a useful indicator of vascular invasion.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Parkinson's disease (PD) patients frequently develop obstructive sleep apnea (OSA). In order to clarify the clinical significance of OSA in PD, we compared descriptive variables between PD ...patients with OSA (PD + OSA) and without (PD − OSA), and between the PD + OSA group and a group of OSA patients without PD (control OSA). The apnea hypopnea index (AHI) cutoff of 15 episodes/hour on polysomnogram (PSG) was used to assign 107 PD patients to groups; OSA-related symptoms and PSG findings were then compared. Demographic and PSG variables were compared between PD + OSA patients and 31 OSA controls. Twenty-four patients with PD (22.4%) were classified as PD + OSA. There were no significant differences in descriptive variables between the PD + OSA and PD − OSA groups. The PD + OSA group had a higher arousal index on PSG than the PD − OSA group, although the two groups had similar ESS scores. The PD + OSA patients had a lower respiratory arousal index and a smaller decrease in oxygen saturation than the control OSA group, despite having a similar AHI. The prevalence of OSA in PD did not differ from that in the general elderly population, indicating that the clinical significance of OSA as a contributor to daytime sleepiness in PD is low.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Microcystins (MCs) are a group of cyclic heptapeptide hepatotoxins produced by
and several other genera of cyanobacteria. Many structural variants have been characterized using various methods such ...as liquid chromatography-mass spectrometry (LC-MS) analysis, enzyme-linked immunosorbent assay (ELISA) and protein phosphatase 2A (PP2A) inhibition assay. The representative MC, MC-LR, and related cyanobacterial toxins strongly inhibit PP2A activity and can therefore be assayed by measuring the extent of PP2A inhibition. However, these methods require reference toxin standards for the quantification and identification of known MCs. To obtain various MC-producing cyanobacterial strains, we surveyed and collected MC-producing cyanobacteria from environmental sources of water in Okinawa, Japan. Using a dual assay (LC-MS analysis and PP2A inhibition assay), we identified and isolated
strains producing five MC variants (MC-LR, -RR, -LA, -FR and -WR). Approximately 4 mg of MC-WR and -FR toxins were purified from the laboratory culture of the
isolate NIES-4344. Pure MC-WR and -FR variants were prepared for future use as toxin standards in LC-MS analysis. Phylogenetic analysis based on
revealed that the NIES-4344 strain belongs to the identified groups in
. This is the first report of
strains producing mainly MC-WR and -FR toxins in Japan.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Aim: Expressions of the myc target genes Mina53 and mimitin are high in esophageal squamous cell carcinoma and colon cancer, and their relationship to cell proliferation and patient prognosis has ...been reported. Because c‐myc gene expression is closely related to hepatocellular carcinoma (HCC) growth or formation and/or maintenance, we examined the Mina53 and mimitin expressions in HCC.
Methods: Surgically resected 53 HCC tissues were immunohistochemically examined for Mina53 and mimitin expressions and their relationship to clinicopathological factors.
Results: Diffuse Mina53 expression was observed in the nuclei of cancer cells in the tumor nodule, but was often strong at the periphery of tumor nodules. Diffuse or scattered expression of mimitin was observed in the cytoplasm of HCC cells in tumor nodules. Mina53 expression was higher in poorly differentiated HCC than in well‐differentiated HCC, and significant relationship to histological grade was observed. The cases with a high Mina53 expression also had a high expression of a proliferation marker MIB‐1. This suggested the involvement of Mina53 in cell proliferation. Mina53 expression was high in the tumors of >2 cm of diameter than in ≤2 cm (P < 0.01). Mimitin expression tended to be high in tumors of >2 cm, but no significant relationship was observed either to histological grade, MIB‐1 expression, or the other clinicopathologic factors.
Conclusions: Our findings suggested that Mina53 expression is accelerated in HCC with a lower histological grade, with cell proliferation capability, or with a larger diameter, and Mina53 is related to biological malignancy of HCC.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK