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11.
12.
High expression of nitric oxide synthases is a favorable prognostic sign in non-small cell lung carcinoma 总被引:2,自引:0,他引:2
Puhakka A Kinnula V Näpänkangas U Säily M Koistinen P Pääkkö P Soini Y 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2003,111(12):1137-1146
Immunohistochemical expression of neuronal (n), endothelial (e), and inducible (i) NOS and their association with the type, grade, apoptotic index, proliferation of tumors and the survival of patients were investigated in 89 biopsies of non-small cell lung carcinoma (NSCLC). In tumor cells, expression of iNOS was detected in 35/89 (40%) cases, while 79/89 (89%) and 72/89 (81%) cases showed weak to intense positivity for eNOS and nNOS, respectively. Strong eNOS staining was seen significantly more often in adenocarcinomas than in squamous cells carcinomas (p=0.016), and iNOS immunoreactivity was seen more often in grade I-II tumors than in grade III tumors (p=0.024). There was no significant difference between the low and high apoptotic indexes or between the low and high proliferation rates of tumors in any instance of NOS staining. The patients with tumors showing high nNOS expression tended to have better survival than the others (p=0.06, log-rank; p=0.04, Bresow; p=0.048, Tarone-Ware). Similarly, the patients with tumors showing high expression of iNOS, eNOS and nNOS, as determined by a combined sum index, had a better survival than those with a low sum index for these enzymes (p<0.05). The results show intense expression of eNOS and nNOS, and moderate expression of iNOS in tumor cells of non-small cell carcinoma. Intense NOSs expression seems to be a favorable prognostic sign in non-small cell lung carcinoma. 相似文献
13.
Serum levels of vitamin D metabolites and the subsequent risk of colon and rectal cancer in Finnish men 总被引:4,自引:0,他引:4
Joseph Tangrea Kathy Helzlsouer Pirjo Pietinen Philip Taylor Bruce Hollis Jarmo Virtamo Demetrius Albanes 《Cancer causes & control : CCC》1997,8(4):615-625
Experimental and human epidemiologic data suggest a protective rolefor vitamin D in large bowel cancer. To investigate this association, weconducted a nested case-control study within a Finnish clinical trial cohort.Cases (n = 146) were participants diagnosed with primary adenocarcinoma ofthe large bowel. Controls were matched (2:1) to cases on age, date ofbaseline blood draw, and study clinic. Prediagnostic serum levels of thevitamin D metabolites, 25-hydroxyvitamin D (25-OH D), and1,25-dihydroxyvitamin D (1,25-DIOHD) were used as primary exposure measures.The baseline geometric-mean serum level of 25-OH D was 11.6 percent lower incases than in controls (12.2 cf 13.8 ug/l, P = 0.01) while serum levels of1,25-DIOH D did not differ by case-control status. No association was seenbetween serum levels of 1,25-DIOH D and large bowel cancer risk. However, theestimated relative risk (RR) of large bowel cancer decreased with increasinglevel of serum 25-OH D and the associa tion was more pronounced for rectalcancer (55 cases; RR by quartile = 1.00, 0.93, 0.77, 0.37; trend P = 0.06).Neither exclusion of early cases nor multivariate adjustment for potentialconfounders materially altered these estimates. There was no evidence ofeffect modification by level of 1,25-dihydroxyvitamin D or with other knownrisk-factors for large bowel cancer. 相似文献
14.
15.
We investigated the occurrence and significance of somatic symptoms in the process leading up to suicide. The material consisted of all individuals who had committed suicide (n=108) in the province of Kuopio during the Finnish National Suicide Prevention Project. Methods of study included semi-structured interviews with workers who had last treated the suicide victim, and consensus case reports based on psychologic autopsy. Nearly half (44%) of the suicide victims, particularly men, had complained of somatic symptoms during their last treatment contact. Seventy-four per cent had contacted health or social services during the month immediately before suicide. Suicide was usually a surprise to workers. Most (79%) of the individuals studied had experienced a marked loss before suicide. More than half of the losses (69%) had occurred during the preceding year. Immediately before suicide, some depressed individuals found it difficult to talk about their depression and the losses that have led to it. They often complain about somatic symptoms instead. Such complaints may be associated with an acute risk of suicide. Awareness of the fact that psychologic and somatic symptoms are connected could facilitate identification of acute risk of suicide and planning of emergency help for and treatment of a patient. 相似文献
16.
Sanna Matilainen Pirjo Isohanni Liliya Euro Tuula L?nnqvist Helena Pihko Tero Kivel? Sakari Knuutila Anu Suomalainen 《European journal of human genetics : EJHG》2015,23(3):325-330
Mutations in SUCLA2, encoding the ß-subunit of succinyl-CoA synthetase of Krebs cycle, are one cause of mitochondrial DNA depletion syndrome. Patients have been reported to have severe progressive childhood-onset encephalomyopathy, and methylmalonic aciduria, often leading to death in childhood. We studied two families, with children manifesting with slowly progressive mitochondrial encephalomyopathy, hearing impairment and transient methylmalonic aciduria, without mtDNA depletion. The other family also showed dominant inheritance of bilateral retinoblastoma, which coexisted with mitochondrial encephalomyopathy in one patient. We found a variant in SUCLA2 leading to Asp333Gly change, homozygous in one patient and compound heterozygous in one. The latter patient also carried a deletion of 13q14 of the other allele, discovered with molecular karyotyping. The deletion spanned both SUCLA2 and RB1 gene regions, leading to manifestation of both mitochondrial disease and retinoblastoma. We made a homology model for human succinyl-CoA synthetase and used it for structure–function analysis of all reported pathogenic mutations in SUCLA2. On the basis of our model, all previously described mutations were predicted to result in decreased amounts of incorrectly assembled protein or disruption of ADP phosphorylation, explaining the severe early lethal manifestations. However, the Asp333Gly change was predicted to reduce the activity of the otherwise functional enzyme. On the basis of our findings, SUCLA2 mutations should be analyzed in patients with slowly progressive encephalomyopathy, even in the absence of methylmalonic aciduria or mitochondrial DNA depletion. In addition, an encephalomyopathy in a patient with retinoblastoma suggests mutations affecting SUCLA2.Mitochondrial diseases are caused by genetic defects in nuclear or mitochondrial DNA (mtDNA) that disrupt function of the respiratory chain, compromising the synthesis of ATP. Most childhood-onset phenotypes are caused by autosomal recessive mutations in nuclear-encoded mitochondrial proteins. Mitochondrial diseases can manifest at any age, with almost any symptom, in almost any tissue, although the tissues with the largest dependence on oxidative energy supply, such as the central nervous system, sensory organs and skeletal muscle,1 are most commonly affected. The wide clinical and genetic heterogeneity with overlapping phenotypes makes the diagnostics of mitochondrial diseases challenging.2mtDNA depletion syndrome is associated with many clinical phenotypes and has a variable genetic background. It can be caused by several nuclear genes, which typically impair mtDNA replication, repair or nucleotide synthesis.3 One of these genes is SUCLA2, encoding the β-subunit of the Krebs cycle enzyme ADP-forming succinyl-CoA synthetase (SCS-A). SCS catalyzes the reversible conversion of succinyl-CoA to succinate, accompanied by substrate-level phosphorylation of ADP or GDP.4 The enzyme is a heterodimer composed of a catalytic α-subunit, encoded by SUCLG1 and a β-subunit that determines the enzymes'' substrate specificity for either ADP (SUCLA2) or GDP (SUCLG2). SCS is widely expressed in mammalian tissues, with predominance of either the ADP- or GDP-forming form in each tissue. SUCLG1 is ubiquitously expressed, whereas expression of SUCLA2 dominates in catabolic tissues, in which the main source of energy is ATP, such as the brain, and is induced in heart and skeletal muscle.4, 5 Patients with SUCLA2 mutations typically have progressive childhood-onset Leigh-like encephalomyopathy associated with dystonia, hypotonia, sensorineural hearing deficit, lesions of the basal ganglia, depletion of mtDNA and methylmalonic aciduria.3, 6 Over 20 patients and five different mutations in SUCLA2 have been described.6, 7, 8, 9, 10We report here molecular basis of mitochondrial encephalomyopathy, also combined with bilateral retinoblastoma, in patients with clinical symptoms or signs previously described in association with SUCLA2 mutations: encephalomyopathy with hearing deficit and methylmalonic aciduria. 相似文献
17.
Knuuti J Takala TO Någren K Sipilä H Turpeinen AK Uusitupa MI Nuutila P 《Diabetologia》2001,44(2):184-187
Abstract
Aims/hypothesis. Fatty acids are an important source of energy in the myocardium. Abnormal myocardial fatty acid metabolism could contribute
to the deterioration of cardiac function frequently observed in patients with Type II (non-insulin-dependent) diabetes mellitus.
In our previous study, myocardial total uptake of non-esterified fatty acid (NEFA) was measured in patients with impaired
glucose tolerance and found to be normal. This study aimed to investigate the subsequent metabolic steps and β-oxidation of NEFA. Methods. A total of 6 men with impaired fasting glucose (age 50 ± 2 years, BMI 29 ± 1 kg/m2, means ± SEM) and 6 healthy men (50 ± 1 years, 25 ± 1 kg/m2) were studied in the fasting state. Myocardial blood flow was measured with [15O]H2O and positron emission tomography and myocardial NEFA metabolism with [11C]palmitic acid. Results. Myocardial blood flow was normal and not different between the impaired glucose tolerance and the control group (78 ± 6 vs
73 ± 13 ml/100 g/min, NS). The [11C]palmitic acid uptake indices were similar between the groups (10.4 ± 0.5 vs 11.2 ± 0.8 ml/100 g/min, respectively, NS).
The clearance of [11C]-palmitate from the myocardium, an index of NEFA β-oxidation, was similar between the groups (half-times of activity 17.6 ± 1.6 vs 19.5 ± 2.3 min, respectively, NS) Conclusion/interpretation. The results indicate that myocardial NEFA uptake and β-oxidation are not altered in patients with IGT. Thus, it is not likely that altered NEFA metabolism contributes to the deterioration
of the cardiac function in patients with IGT or Type II diabetes. [Diabetologia (2001) 44: 184–187]
Received: 9 June 2000 and in revised form: 25 September 2000 相似文献
18.
Enhancement of insulin-stimulated myocardial glucose uptake in patients with Type 2 diabetes treated with rosiglitazone. 总被引:3,自引:0,他引:3
K. Hllsten K. A. Virtanen F. Lnnqvist T. Janatuinen M. Turiceanu T. Rnnemaa J. Viikari T. Lehtimki J. Knuuti P. Nuutila 《Diabetic medicine》2004,21(12):1280-1287
AIMS: Peroxisome proliferator-activated receptor gamma (PPARgamma) activators have recently been identified as regulators of cellular proliferation, inflammatory responses and lipid and glucose metabolism. These agents prevent coronary arteriosclerosis and improve left ventricular remodelling and function in heart failure after myocardial infarction. Improvement in myocardial metabolic state may be one of the mechanisms behind these findings. The aim of this study was to investigate the effects of rosiglitazone on myocardial glucose uptake in patients with Type 2 diabetes. Placebo and metformin were used as control treatments. METHODS: Forty-four patients were randomized to treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.) or placebo in a 26-week double-blinded trial. Myocardial glucose uptake was measured using [(18)F]-2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and positron emission tomography (PET) during euglycaemic hyperinsulinaemia before and after the treatment. RESULTS: Rosiglitazone increased insulin-stimulated myocardial glucose uptake by 38% (from 38.7 +/- 3.4 to 53.3 +/- 3.6 micromol 100 g(-1) min(-1), P = 0.004) and whole body glucose uptake by 36% (P = 0.01), while metformin treatment had no significant effect on myocardial (40.5 +/- 3.5 vs. 36.6 +/- 5.2, NS) or whole body glucose uptake. Myocardial work as determined by the rate-pressure-product was similar between the groups. Neither treatment had any significant effect on fasting serum free fatty acids (FFA) but the FFA levels during hyperinsulinaemia were more suppressed in the rosiglitazone group (-47%, P = 0.02). Myocardial glucose uptake correlated inversely to FFA concentrations both before (r =-0.54, P = 0.002) and after (r = -0.43, P = 0.01) the treatment period in the pooled data. Furthermore, the increase in myocardial glucose uptake correlated inversely with interleukin-6 (IL-6) concentrations (r = -0.58, P = 0.03). CONCLUSIONS: In addition to the improvement in whole body insulin sensitivity, rosiglitazone treatment enhances insulin stimulated myocardial glucose uptake in patients with Type 2 diabetes, most probably due to its suppression of the serum FFAs. 相似文献
19.
Anna Viitasalo Timo A. Lakka David E. Laaksonen Kai Savonen Hanna-Maaria Lakka Maija Hassinen Pirjo Komulainen Tuomo Tompuri Sudhir Kurl Jari A. Laukkanen Rainer Rauramaa 《Diabetologia》2014,57(5):940-949
Aims/hypothesis
We validated the metabolic syndrome (MetS) score by confirmatory factor analysis (CFA) in children, middle-aged men, and older women and men and by investigating the relationships of the MetS score to incident type 2 diabetes, myocardial infarction, and cardiovascular and overall death in middle-aged men.Methods
We assessed the core features of MetS, calculated the MetS score using z scores for waist circumference, insulin, glucose, triacylglycerols, HDL-cholesterol and blood pressure, and carried out CFA to investigate whether MetS represents a single entity in population samples of 491 children, 1,900 middle-aged men, 614 older women and 555 older men from Finland. We also followed-up incident type 2 diabetes for 11 years and other outcomes for 17–18 years in middle-aged men.Results
We carried out second-order CFAs in which the MetS was represented by a second-order latent variable underlying four latent variables characterised by abdominal obesity, insulin resistance, dyslipidaemia and raised blood pressure in different age groups. These second-order factors and factors derived from first-order CFA using previously proposed models were strongly associated with a composite MetS score in all age groups (r?=?0.84–0.94) and similarly predicted type 2 diabetes, cardiovascular outcomes and mortality in middle-aged men. The risk of type 2 diabetes, myocardial infarction, cardiovascular death and overall death increased 3.67-, 1.38-, 1.56- and 1.44-fold, respectively, for a 1 SD increase in the MetS score.Conclusions
The MetS can be described as a single entity in all age groups. The MetS score is a valid tool for research evaluating cardiometabolic risk in different age groups. Further research is needed to define cut-off points for risk estimation in clinical practice. 相似文献20.