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1Relevance of α-defensins(HNP1-3) and defensin β-1 in diabetes显示文摘AIM: To investigate the genetic background of human defensin expression in type 1 and 2 diabetes.METHODS: Associations between DEFA1/DEFA3 gene copy number polymorphism and diabetes as well as between the promoter polymorphisms of DEFB1 and diabetes were studied. The copy number variation of the DEFA1/DEFA3 genes was determined in 257 diabetic patients(117 patients with type 1 and 140 with type 2 diabetes). The control group consisted of 221 age- and gender-matched healthy blood donors. The cumulative copy numbers of the DEFA1/DEFA3 genes were detected by using quantitative PCR analysis. To evaluate the HNP 1-3(human neutrophil peptide 1-3 or α-defensin) levels in the circulation, plasma HNP 1-3 concentrations were measured by ELISA. The expression of DEFA1/A3 in peripheral leukocytes of the diabetic patients was measured by quantitative RT PCR analysis. Three SNPs of the human DEFB1(human defensin β-1) gene: DEFB1 G-20A(rs11362), DEFB1 C-44G(rs1800972) and DEFB1 G-52A(rs1799946) were genotyped by Custom TaqMan? Real Time PCR assay.RESULTS: Significant differences were observed in HNP1-3 levels between the healthy subjects and both groups of diabetic patients. The mean ± SE was 28.78 ± 4.2 ng/mL in type 1 diabetes, and 29.82 ± 5.36 ng/mL in type 2 diabetes, vs 11.94 ± 2.96 ng/mL in controls; P < 0.01 respectively. There was no significant difference between patients with type 1 and type 2 diabetes in the high plasma concentrations of HNP1-3. The highest concentrations of α-defensin were found in diabetic patients with nephropathy(49.4 ± 4.8 ng/mL), neuropathy(38.7 ± 4.8 ng/mL) or cardiovascular complications(45.6 ± 1.45 ng/L). There was no significant difference in the cumulative copy numbers of DEFA1/DEFA3 genes between controls and patients, or between patients with the two types of diabetes. Comparisons of HNP 1-3 plasma level and DEFA1/A3 copy number of the same patient did not reveal significant relationship between defensin-α levels and the gene copy numbers(r2 = 0.01). Similarly, no positive correlation was observed between the copy numbers and the mRNA expression levels of DEFA1/A3. Regarding the C-44G polymorphism of DEFB1, the GG 'protective' genotype was much less frequent(1%-2%) among both groups of patients than among controls(9%).CONCLUSION: Elevated HNP1-3 levels in diabetes are independent of DEFA1/DEFA3 copy numbers, but GG genotype of C-44G SNP in DEFB1 gene may result in decreased defensin β-1 production.Balázs Csaba Németh Tamás Várkonyi Ferenc Somogyvári Csaba Lengyel Katalin Fehértemplomi Szabolcs Nyiraty Péter Kempler Yvette Mándi 2014World Journal of Gastroenterology2014,20,27:4
2Autonomic and sensory nerve dysfunction in primary biliary cirrhosis显示文摘AIM: Cardiovascular autonomic and peripheral sensory neuropathy is a known complication of chronic alcoholic and non-alcoholic liver diseases. We aimed to assess the prevalence and risk factors for peripheral sensory nerve and autonomic dysfunction using sensitive methods in patients with primary biliary cirrhosis (PBC). METHODS: Twenty-four AMA M2 positive female patients with clinical, biochemical and histological evidence of PBC and 20 age matched healthy female subjects were studied. Five standard cardiovascular reflex tests and 24-h heart rate variability (HRV) analysis were performed to define autonomic function. Peripheral sensory nerve function on median and peroneal nerves was characterized by current perception threshold (CPT), measured by a neuroselective diagnostic stimulator (Neurotron, Baltimore, MD). RESULTS: Fourteen of 24 patients (58%) had at least one abnormal cardiovascular reflex test and thirteen (54%) had peripheral sensory neuropathy. Lower heart rate response to deep breathing (P=0.001), standing (P=0.03) and Valsalva manoeuvre (P=0.01), and more profound decrease of blood pressure after standing (P=0.03) was found in PBC patients than in controls. As a novel finding we proved that both time domain and frequency domain parameters of 24-h HRV were significantly reduced in PBC patients compared to controls. Each patient had at least one abnormal parameter of HRV. Lower CPT values indicated hyperaesthesia as a characteristic feature at peroneal nerve testing at three frequencies (2000 Hz: P=0.005; 250 Hz: P=0.002; 5 Hz: P=0.004) in PBC compared to controls. Correlation of autonomic dysfunction with the severity and duration of the disease was observed. Lower total power of HRV correlated with lower CPT values at median nerve testing at 250 Hz (P = 0.0001) and at 5 Hz (P=0.002), as well as with those at peroneal nerve testing at 2000 Hz (P=0.01). CONCLUSION: Autonomic and sensory nerve dysfunctions are frequent in PBC. Twenty-four-hour HRV analysis is more sensitive than standard cardiovascular tests for detecting of both parasympathetic and sympathetic impairments. Our novel data suggest that hyperaesthesia is a characteristic feature of peripheral sensory neuropathy and might contribute to itching in PBC. Autonomic dysfunction is related to the duration and severity of PBC.Katalin Keresztes lldikó Istenes Aniko Folhoffer Peter L Lakatos Andrea Horvath Timea Csak Peter Varga Peter Kempler Ferenc Szalay 2004World Journal of Gastroenterology2004,10,20:2
3Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid:a meta-analysis显示文摘Ziegler D Nowak H Kempler P 2004Diabet Med2004,21,2:1
4Actinidia arguta:Characteristics relevant to commercial production显示文摘KABALUK J T KEMPLER C TOIVONEN P M A 1997Fruit Varieties Journal1997,51,2:1
5Disconnection and cerebral metabolism: The case of conduction aphasia显示文摘Kempler D Metter EJ Jackson CA 1988Arch Neurol1988,45,3:1
6Treatment of symptomatic diabetic polyneuropathy with the antioxidanta- lipoic acid; a meta- analysis显示文摘Ziegler D Nowak H Kempler P 2004Diabet Meal2004,21,2:1
7Treatment of symptomatic diabetic peripheral neuropathy with the protein kinase C beta-inhibitor ruboxistaurin mesylate during a 1-year,randomized,placebo-controlled,double-blind clinical trial显示文摘 Bril V Kempler P 2005Clin Ther2005,27,8:1
8Peripheral sen-sory nerve dysfunction in children and adolescents with Type 1 diabetes mellitus显示文摘Barkai L Kempler P Vámosi I 0,,:1
9Current issues in achievement goal theory and research显示文摘Paul R. Pintrich AnneMarie M. Conley Toni M. Kempler 2004International Journal of Educational Research2004,,4:1
10Treatment of symptomatic diabetic neuropathy with the antioxidant alpha-Lipoicacid:a meta-analysis显示文摘 Nowak H Kempler P 2004Diabetic Med2004,21,2:1
11Treatment of symp- tomatic diabetic polyneuropathy with the antioxidant al- pha-lipoic acid : a meta-analysis 显示文摘Ziegler D Nowak H Kempler P 2004Diabet Med2004,21,2:1
12Treatment of symptomatic dia- betic polyneuropathy with the antioxidant alpha-lipoic acid:a meta-a-nalysis显示文摘Zicgler D Nowak H Kempler P 2004Diabet Med2004,21,:1
13Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid:a meta-analysis显示文摘Ziegler D Nowak H Kempler P 2004Diabet Med2004,21,2:1
14The pathogenesis of diabetic and hepatic neuropathies显示文摘Winkler G Kempler P 2001Orv Hetil2001,142,:1
15Disconnection and cerebral metabolism:The case of conduction aphasia显示文摘Kempler D Metter EJ Jackson CA 1988Arch Neurology1988,45,3:1
16Peripheral sensorynerve dysfunction in children and adolescents with type 1 diabetes mellitus 显示文摘Barkai L Kempler P Vamosi I 1998Diabet Med1998,15,3:1
17Treatment of symptomatic diabetic polyneuropathy with the antioxidant α-lipoic acid:a meta analysis显示文摘Ziegler D Nowak H Kempler P 2004Diabet Med2004,21,:1
18Auto nomic neuropathy is associated with increased cardio vascular risk factorszthe EURODIAB IDDM Complications Study 显示文摘Kempler P Tesfaye S Chaturvedi N 2002Diabet Med2002,19,:1
19Treatment of symptomatic dia- betic polyneuropathy with the antioxidant oL-lipoie aeid:a meta anal- ysis 显示文摘Ziegler D Nowak H Kempler P 2004Diabet Med2004,21,2:1
20Biochemistry and genetics of citrate utilization in Streptococcus lactis ssp diacetylactis 显示文摘KEMPLER G M MC KAY L L 1981J Dairy Sci1981,64,:1
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