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991.
Tyynelä J Cooper JD Khan MN Shemilts SJ Haltia M 《Brain pathology (Zurich, Switzerland)》2004,14(4):349-357
The neuronal ceroid-lipofuscinoses (NCLs) are recessively inherited lysosomal storage diseases, currently classified into 8 forms (CLN1-CLN8). Collectively, the NCLs constitute the most common group of progressive encephalopathies of childhood, and present with visual impairment, psychomotor deterioration and severe seizures. Despite recent identification of the underlying disease genes, the mechanisms leading to neurodegeneration and epilepsy in the NCLs remain poorly understood. To investigate these events, we examined the patterns of storage deposition, neurodegeneration, and glial activation in the hippocampus of patients with CLN1, CLN2, CLN3, CLN5 and CLN8 using histochemistry and immunohistochemistry. These different forms of NCL shared distinct patterns of neuronal degeneration in the hippocampus, with heavy involvement of sectors CA2-CA4 but relative sparing of CA1. This selective pattern of degeneration was also observed in immunohistochemically identified interneurons, which exhibited a graded severity of loss according to phenotype, with calretinin-positive interneurons relatively spared. Furthermore, glial activation was also regionally specific, with microglial activation most pronounced in areas of greatest neuronal loss, and astrocyte activation prominent in areas where neuronal loss was less evident. In conclusion, the NCLs share a common pattern of selective hippocampal pathology, distinct from that seen in the majority of temporal lobe epilepsies. 相似文献
992.
993.
Todorova B Kubaszek A Pihlajamäki J Lindström J Eriksson J Valle TT Hämäläinen H Ilanne-Parikka P Keinänen-Kiukaanniemi S Tuomilehto J Uusitupa M Laakso M;Finnish Diabetes Prevention Study 《The Journal of clinical endocrinology and metabolism》2004,89(5):2019-2023
In population-based studies, dyslipidemia related to insulin resistance (high triglyceride level and low high-density lipoprotein cholesterol level) is a risk factor for type 2 diabetes. Therefore, variants in genes regulating lipid and lipoprotein metabolism are potential candidate genes for diabetes. We investigated whether the G-250A polymorphism of the hepatic lipase gene (LIPC) predicts the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. This study randomized subjects to either the intervention group (lifestyle modification aimed at weight loss, such as changes in diet and increased physical exercise) or the control group. Genotyping at position -250 of the LIPC gene was performed with PCR amplification, DraI enzyme digestion, and gel electrophoresis in 490 subjects with IGT whose DNA was available. In the entire study population, the conversion rate to type 2 diabetes was 17.8% among subjects with the G-250G genotype and 10.7% among subjects with the -250A allele (P = 0.032). In univariate analysis, the odds ratio for the G-250G genotype to predict the conversion from IGT to type 2 diabetes was 1.80 (95% confidence interval, 1.05-3.10; P = 0.034). In multivariate logistic regression analysis, the G-250G genotype predicted the conversion to diabetes independently of the study group (control or intervention), gender, weight, waist circumference at baseline, and change in weight and waist circumference. In the intervention group, 13.0% of subjects with the G-250G genotype and 1.0% of the subjects with the -250A allele converted to diabetes (P = 0.001). We conclude that the G-250G genotype of the LIPC gene is a risk factor for type 2 diabetes. Therefore, genes regulating lipid and lipoprotein metabolism may be potential candidate genes for type 2 diabetes. 相似文献
994.
BACKGROUND: Although alcohol abuse is known to create a variety of adverse effects on hematopoiesis, the associations between ethanol consumption and hematological abnormalities have not been fully established. METHODS: We studied 144 consecutive adult patients who underwent clinical and bone marrow examinations due to abnormal findings in peripheral blood cell counts or red blood cell indices without previously established diagnoses of specific hematological diseases, malignancies, or infections. Assessment included the amount of alcohol consumption, complete blood cell counts, morphological review of peripheral blood and bone marrow, markers of liver status, and erythrocyte folate and serum vitamin B12 levels. RESULTS: There were 57 (40%) patients who showed a history of hazardous drinking and 87 patients who were either nondrinkers or social drinkers. The incidence of anemia was 51% in the alcohol abusers, as compared with 69% of the nonalcoholics (p < 0.05). A diverse pattern of hematological effects was observed in the alcohol abusers. Abnormal platelet and leukocyte levels were common, especially in the anemic alcoholics. Both increased mean cell volume of erythrocytes (macrocytosis; 67 vs. 18%; p < 0.0001) and mean cell hemoglobin (63 vs. 22%; p < 0.0001) were more frequent in the alcoholics than in the nonalcoholics. Reticulocytosis (37%), thrombocytopenia (41%), and combined cytopenias (34-38%) were also common findings in the alcoholic patients. The blood smears from such patients typically showed round macrocytes, stomatocytes, and knizocytes. Bone marrow aspirates revealed vacuolization of pronormoblasts in 24% of the alcoholic patients. Interestingly, megakaryocytes in the cell periphery were also vacuolized in 20% of the alcohol abusers, especially in those with recent intoxication. CONCLUSIONS: Our findings suggest that alcohol abuse results in diverse patterns of hematological effects and affects several cell lines. Therefore, in patients undergoing bone marrow examinations due to cytopenias, the probabilities for likely findings seem to be different between alcoholics and nonalcoholics. Information on ethanol consumption should be systematically included in the clinical assessment of such patients. 相似文献
995.
Timonen M Horrobin D Jokelainen J Laitinen J Herva A Räsänen P 《Journal of affective disorders》2004,82(3):447-452
BACKGROUND: Since low fish consumption and omega-3 fatty acids have recently been linked with depression, we investigated by means of a large, general population database, whether a low fish consumption is associated with increased risk of developing depression. METHODS: The Northern Finland 1966 Birth Cohort was followed up prospectively from pregnancy up to the age of 31 years. The data on HSCL-25 depression subscale, doctor-diagnosed life-time depression and fish consumption (during the previous 6 months) of cohort members were obtained by postal questionnaires at the age of 31. The final number of cohort members, whose completed variable information was available in multivariate logistic analyses, was 2721 males and 2968 females. RESULTS: After adjusting for body mass index, serum total cholesterol level and socioeconomic situation, logistic regression analyses showed that among females the risk of developing depression increased up to 2.6-fold (95%CI 1.4-5.1) among rare fish eaters when compared with regular eaters. In males, there were no significant differences between rare and regular fish eaters for any of the estimates of depression. LIMITATIONS: The data on life-time fish consumption of cohort members were not available. CONCLUSIONS: A low frequency of fish consumption was statistically significantly associated with depression in women, but not in men. Possible background-theories behind the gender difference are discussed. 相似文献
996.
Hyperlipidemia in persons using antipsychotic medication: a general population-based birth cohort study 总被引:3,自引:0,他引:3
Saari K Koponen H Laitinen J Jokelainen J Lauren L Isohanni M Lindeman S 《The Journal of clinical psychiatry》2004,65(4):547-550
BACKGROUND: Shortly after phenothiazines were introduced, they were found to elevate serum triglyceride and total cholesterol levels. During the past decade, an increasing body of literature has also documented this effect in atypical antipsychotics. Previous studies of antipsychotic-associated hyperlipidemias are based on clinical samples, mostly from case series. We studied the prevalence of hyperlipidemia in subjects who did and did not take antipsychotic medication in a prospective, general population-based birth cohort. METHOD: The study sample consisted of 5654 members of the unselected Northern Finland 1966 Birth Cohort who participated in the 1997-1998 clinical examination at 31 years of age. Blood samples were taken after an overnight fast, and serum total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels were determined. Health habits and other possible correlates for hyperlipidemia were assessed using a questionnaire. The sample was analyzed in 4 categories according to use of antipsychotic medication: (1) atypical, (2) typical, (3) atypical and typical (for the 3 antipsychotic categories, total N = 45), and (4) no antipsychotic medication (N = 5609). Nonparametric tests and multiple logistic regression analysis were used to measure the effect of antipsychotics on serum lipids. RESULTS: High lipid levels were found in persons treated with both atypical and typical medication (mean total cholesterol = 233 mg/dL, mean triglycerides = 163 mg/dL). Mean total cholesterol and triglycerides were also high in subjects who used only typical medication (215 mg/dL and 148 mg/dL, respectively). The prevalence of hypercholesterolemia, high LDL cholesterol, and hypertriglyceridemia was high in persons using antipsychotic medication (31.1%, 20.0%, and 22.2%, respectively) compared with persons not using such medication (12.2%, 10.2%, and 7.0%, respectively). After we adjusted for risk factors for hyperlipidemia (sex, diet, waist circumference, physical exercise, smoking, and alcohol consumption), the results of logistic regression analysis showed that in persons treated with antipsychotic medication the risk of hypercholesterolemia was 2.8 (95% CI = 1.4 to 5.6); of hypertriglyceridemia, 2.3 (95% CI = 1.0 to 5.4); and of high LDL cholesterol, 1.6 (95% CI = 0.7 to 3.5). CONCLUSION: Lipid levels in subjects who used both atypical and typical medication and those who used only typical medication were high even in young age. As these persons are at special risk of hyperlipidemia, their lipid levels should be regularly monitored, and a cholesterol-lowering diet, as well as medication, should be considered. The results indicate an elevated risk of hyperlipidemia in persons using antipsychotic medication independent of the other risk factors assessed. 相似文献
997.
Nijssen PC Ceuterick C van Diggelen OP Elleder M Martin JJ Teepen JL Tyynelä J Roos RA 《Brain pathology (Zurich, Switzerland)》2003,13(4):574-581
We describe the neuropathological and biochemical autopsy findings in 3 patients with autosomal dominant adult neuronal ceroid lipofuscinosis (ANCL, Parry type; MIM 162350), from a family with 6 affected individuals in 3 generations. Throughout the brain of these patients, there was abundant intraneuronal lysosomal storage of autofluorescent lipopigment granules. Striking loss of neurons in the substantia nigra was found. In contrast, little neuronal cell loss occurred in other cerebral areas, despite massive neuronal inclusions. Visceral storage was present in gut, liver, cardiomyocytes, skeletal muscle, and in the skin eccrine glands. The storage material showed highly variable immunoreactivity with antiserum against subunit c of mitochondrial ATP synthase, but uniform strong immunoreactivity for saposin D (sphingolipid activating protein D). Protein electrophoresis of isolated storage material revealed a major protein band of about 14 kDa, recognized in Western blotting by saposin D antiserum (but not subunit c of mitochondrial ATPase (SCMAS) antiserum). Electron microscopy showed ample intraneuronal granular osmiophilic deposits (GRODs), as occurs in CLN1 and congenital ovine NCL. These forms of NCL are caused by the deficiencies of palmitoyl protein thioesterase 1 and cathepsin D, respectively. However, activities of these enzymes were within normal range in our patients. Thus we propose that a gene distinct from the cathepsin D and CLN1-CLN8 genes is responsible for this autosomal dominant form of ANCL. 相似文献
998.
OBJECTIVE: The intensity of climacteric symptoms and their connection with sociodemographic background data were assessed among women who are or will soon be menopausal. METHODS: A sample of 5510 Finnish women who were 42-46 or 52-56-years-old was selected to this 'Quality of Life among Middle-aged Women' Study and received a menopause-specific questionnaire. RESULTS: Only 5% of the older and 36% of the younger women were totally asymptomatic. Altogether, 2% of the younger and 11% of the older women had severe climacteric symptoms. In the younger age group, a high symptom intensity was associated with living in town, having a low level of professional education, and being unemployed/laid off, whereas in the older age group, the experience of severe symptoms was associated with those having a couple relationship. CONCLUSION: Altogether 95% of women in the productive working age (52-56-years-old) surprisingly suffer from mild, moderate, or severe climacteric symptoms. Further even up to 64% of the younger women (42-46-years-old) suffered from similar symptoms. 相似文献
999.
Anttila P Järvi K Latvala J Blake JE Niemelä O 《Clinica chimica acta; international journal of clinical chemistry》2003,338(1-2):45-51
BACKGROUND: The detection of excessive alcohol consumption by laboratory methods continues to lack sensitivity and specificity. Recent studies have suggested that diagnostic improvement may be achieved by combining carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GT) measurements into a marker defined as gamma-CDT. METHODS: We developed a new approach for determining gamma-CDT by using the data obtained from the Axis %CDT turbidimetric assays. Marker results were compared in the assessment of 65 alcoholics, who were either with (n=34) or without (n=31) liver disease, as analysed by clinical, laboratory, and morphological criteria. Reference individuals were 45 healthy volunteers who were either social drinkers or abstainers. RESULTS: Gamma-GT and CDT results derived from both CDTect and %CDT measurements were used to calculate marker ratios as follows 0.8 x ln(GT)+1.3 x ln(CDT). With the established cut-off of 4.0 for the gamma-%CDT, the sensitivity of this method was 94% for men and 82% for women, as compared to 61% and 46% for %CDT and 70% and 73% for GT. The gamma-%CDT method was less dependent on liver status than the various other markers and showed the highest correlation with self-reported alcohol consumption (r=0.7254). CONCLUSIONS: The data indicates that the new gamma-%CDT method yields improved diagnostic accuracy for the detection of excessive ethanol consumption. 相似文献
1000.