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Biomedical subjects

A Lehtonen

Publications and source records attributed to A Lehtonen.

At least 19 recordsLinked to original sources
PubMed2003

Decline in out-of-hospital coronary heart disease deaths has contributed the main part to the overall decline in coronary heart disease mortality rates among persons 35 to 64 years of age in Finland: the FINAMI study.

BACKGROUND: Out-of-hospital deaths constitute the majority of all coronary heart disease (CHD) deaths and are therefore of considerable public health significance. METHODS AND RESULTS: We used population-based myocardial infarction register data to examine trends in out-of-hospital CHD deaths in Finland during 1983 to 1997. We included in out-of-hospital deaths also deaths in the emergency room and all deaths within 1 hour after the onset of symptoms. Altogether, 3494 such events were included in the analyses. The proportion of out-of-hospital deaths of all CHD deaths depended on age and gender. In the age group 35 to 64 years, it was 73% among men and 60% among women. These proportions did not change during the study. The annual average decline in the age-standardized out-of-hospital CHD death rate was 6.1% (95% CI, -7.3, -5.0%) among men and 7.0% (-10.0, -4.0%) among women. These declines contributed among men 70% and among women 58% to the overall decline in CHD mortality rate. In all, 58% of the male and 52% of the female victims of out-of-hospital CHD death had a history of symptomatic CHD. Among men with a prior history of myocardial infarction, the annual average decline in out-of-hospital CHD deaths was 5.3% (-7.2, -3.2%), and among men without such history the decline was 2.9% (-4.4, -1.5%). Among women, the corresponding changes were -7.8% (-14.2, -1.5%) and -4.5% (-8.0, -1.0%). CONCLUSIONS: The decline in out-of-hospital CHD deaths has contributed the main part to the overall decline in CHD mortality rates among persons 35 to 64 years of age in Finland.

Adult↗
PubMed2003

Trends in coronary events in Finland during 1983-1997. The FINAMI study.

AIMS: To analyse the trends in incidence, recurrence, case fatality, and treatments of acute coronary events in Finland during the 15-year period 1983-97. METHODS AND RESULTS: Population-based MI registration has been carried out in defined geographical areas, first as a part of the FINMONICA Project and then continued as the FINAMI register. During the study period, 6501 coronary heart disease (CHD) events were recorded among men and 1778 among women aged 35-64 years. The CHD mortality declined on average 6.4%/year (95% confidence interval -5.4, -7.4%) among men and 7.0%/year (-4.7, -9.3%) among women. The mortality from recurrent events declined even more steeply, 9.9%/year (-8.3, -11.4%) among men and 9.3%/year (-5.1, -13.4%) among women. The proportion of recurrent events of all CHD events also declined significantly in both sexes. Of all coronary deaths, 74% among men and 61% among women took place out-of-hospital. The decline in 28-day case fatality was 1.3%/year (-0.3, -2.3%) among men and 3.1%/year (-0.7, -5.5%) among women. CONCLUSIONS: The study period was characterized by a marked reduction in the occurrence of recurrent CHD events and a relatively modest reduction in the 28-day case fatality. The findings suggest that primary and secondary prevention have played the main roles in the decline in CHD mortality in Finland.

Adult↗
PubMed2001

On the reactions of bisdiolatotungsten(VI) phenoxides. Syntheses, characterizations, and molecular structures of trans-[WCl(2)(Diol)(OAr)(2)].

Coordinated phenoxide groups in [W(eg)(2)(mephe)(2)] (2a) and [W(eg)(2)(prphe)(2)] (2c) (eg = ethanediolate dianion; mephe = OC(6)H(3)Me(2)-2,6; prphe = OC(6)H(3)(i)Pr(2)-2,6) undergo reaction with Br(2), leading to substitution at the para position of the phenyl rings and formation of the complexes [W(eg)(2)(OC(6)H(2)R(2)-2,6-Br-4)(2)] (2b, R = Me; 2d, R = (i)Pr). The reaction of complexes 2a-2d and [W(eg)(2)(buphe)(2)] (2e) (buphe = OC(6)H(3)tBu(2)-2,4) with HCl leads to the displacement of one bidentate diolato ligand from the complex unit and formation of the corresponding trans dichloro diolato bis(phenoxide) tungsten(VI) complex [WCl(2)(eg)(OAr)(2)] (3). The X-ray crystal structure determinations of these compounds confirmed that all complexes 3 have a similar gross structure in which the chloro ligands are arranged at trans positions.

Journal Article↗
PubMed2000

Influenza A and sendai viruses induce differential chemokine gene expression and transcription factor activation in human macrophages.

Chemokines regulate leukocyte traffic and extravasation into the site of inflammation. Here we show that influenza A- or Sendai virus-infected human macrophages produce MIP-1alpha, MIP-1beta, RANTES, MCP-1, MCP-3, MIP-3alpha, IP-10, and IL-8, whereas no upregulation of MIP-3beta, eotaxin, or MDC production was detected. Influenza A virus was a better inducer of MCP-1 and MCP-3 production than Sendai virus, whereas MIP-1alpha, MIP-1beta, RANTES, MIP-3alpha, and IL-8 were induced preferentially by Sendai virus. Infection in the presence of protein synthesis inhibitor indicated that ongoing protein synthesis was required for influenza A virus-induced expression of MCP-1, MCP-3, and IP-10 genes, whereas Sendai virus-induced chemokine mRNA expression took place in the absence of de novo protein synthesis. Neutralization of virus-induced IFN-alpha/beta resulted in downregulation of virus-induced IP-10, MCP-1, and MCP-3 mRNA expression. IFN-alpha or IFN-gamma were found to directly enhance MCP-1, MCP-3, and IP-10 mRNA expression. Both influenza A and Sendai viruses similarly activated transcription factor NF-kappaB. In contrast to NF-kappaB, IRFs and STATs, the other transcription factors involved in the regulation of chemokine gene expression, were differentially activated by these viruses. Influenza A virus more efficiently activated ISGF3 complex formation and Stat1 DNA-binding compared to Sendai virus, which in turn was a more potent activator of IRF-1. Our results show that during viral infections macrophages predominantly produce monocyte and Th1 cell attracting chemokines. Furthermore, virus-induced IFN-alpha/beta enhanced chemokine gene expression in macrophages emphasizing the role of IFN-alpha/beta in the development of Th1 immune responses.

Cells, Cultured↗
PubMed2000

Long-term predictors of stroke in a cohort of people aged 70 years.

This paper aims at studying the development and the risk factors for stroke prospectively during a 6-year follow-up in the Turku Elderly Study, Turku, Finland. The study cohort consisted of 1032 people aged 70 years at baseline. The stroke events (ICD-9 codes 430-434) were identified by computer linkage from the hospital discharge and death registers, and from a follow-up questionnaire. During the 6 years of follow-up, 71 patients (6.9%) suffered a stroke. Previous stroke (RR 5.82), history of transient ischemic attack (RR 4.14), diabetes mellitus (RR 2.50), poorly controlled hypertension (RR 2.42), smoking (RR 1.94) and male sex (RR 1.65) were independent risk factors for stroke. Atrial fibrillation, cardiac failure and previous myocardial infarction did not appear to be significant independent predictors of stroke in the elderly. The risk of stroke in the elderly population appears to be strongly related to the concomitant clinical disease, and this should be remembered when identifying persons at increased risk of stroke. Poorly controlled hypertension was associated with an increased risk of stroke. Thus, achieving a good control of blood pressure in elderly hypertensives receiving treatment has the potential to prevent strokes.

Journal Article↗
PubMed2000

Unusual 9-->10 rearrangement of the substituted cage carbon in the ferratricarbollide series. Synthesis of the isomeric complexes [2-eta 5-(C5H5)-10-X-closo-2,1,7,10-FeC3B8H10] (where X = H2N, MeHN, Me2N, and ButHN).

Treatment of the zwitterionic amine tricarbollides of general formula 7-L-nido-7,8,9-C3B8H10 (1) (where L = Me2HN (1c) and ButH2N (1d)) with [(eta 5-C5H5)Fe(CO)2]2 in refluxing mesitylene resulted in the formation of a mixture of the known compounds [2-(eta 5-C5H5)-9-X-closo-2,1,7,9-FeC3B8H10] (2) (where X = H2N (2a), Me2N (2c), and ButHN (2d)) and a series of new, isomeric ferratricarbollylamines [2-(eta 5-C5H5)-10-X-closo-2,1,7,10-FeC3B8H10] (3) (where X = H2N (3a), Me2N (3c), and ButHN (3d)) in moderate yields. Complexes of type 3 (where X = H2N (3a), MeHN (3b), Me2N (3c), and ButHN (3d)) were also obtained readily by heating complexes of type 2 (where X = H2N (2a), MeHN (2b), Me2N (2c), ButHN (2d), and Bu(t)(Me)N (2e)) at ca. 300 degrees C for 10 min. All the complexes of type 3 contain reactive amine functions in meta positions with respect to the metal center. The observed 9-->10 rearrangement of the substituted cluster carbon is quite unexpected and is believed to result from higher thermodynamic stability of the 10-substituted isomers. The structures of all compounds of type 3 were established by high-field NMR spectroscopy and mass spectrometry, and that of 3d was determined by an X-ray diffraction study.

Journal Article↗
PubMed2000

Lactobacilli and Streptococci activate NF-kappa B and STAT signaling pathways in human macrophages.

Gram-positive bacteria induce the production of several cytokines in human leukocytes. The molecular mechanisms involved in Gram-positive bacteria-induced cytokine production have been poorly characterized. In this work we demonstrate that both nonpathogenic Lactobacillus rhamnosus GG and pathogenic Streptococcus pyogenes (group A streptococci) induce NF-kappa B and STAT DNA-binding activity in human primary macrophages as analyzed by EMSA. NF-kappa B activation was rapid and was not inhibited by a protein synthesis inhibitor cycloheximide, suggesting that these bacteria could directly activate NF-kappa B. STAT1, STAT3, and IFN regulatory factor-1 DNA binding was induced by both bacteria with delayed kinetics compared with NF-kappa B. In addition, streptococci induced the formation of IFN-alpha-specific transcription factor complex and IFN-stimulated gene factor-3 (ISGF3). STAT1 and STAT3 activation and ISGF3 complex formation were inhibited by cycloheximide or by neutralization with IFN-alpha/beta-specific Abs. Streptococci were more potent than lactobacilli in inducing STAT1, ISGF3, and IFN regulatory factor-1 DNA binding. Accordingly, only streptococci induced IFN-alpha production. The activation of the IFN-alpha signaling pathway by streptococci could play a role in the pathogenesis of these bacteria. These results indicate that extracellular Gram-positive bacteria activate transcription factors involved in cytokine signaling by two mechanisms: directly, leading to NF-kappa B activation, and indirectly via cytokines, leading to STAT activation.

Binding Sites↗
PubMed2000

Interferon-induced gene expression and signaling in human hepatoma cell lines.

BACKGROUND/AIM: Interferon(IFN)-alpha alone or combined with other antiviral substances has been extensively used for the treatment of viral infections of the liver. Since the molecular mechanisms of IFN action in liver cells are relatively poorly characterized, we studied IFN-induced gene expression and signaling in human hepatoma, HepG2 and HuH7 cell lines. METHODS/RESULTS: IFN binding to its specific cell surface receptor leads to activation of the Janus family tyrosine kinase (JAK) - signal transducer and activator of transcription (STAT) pathway. We observed that in HepG2 and HuH7 cells IFN-inducible genes were upregulated by IFNs, but relatively high concentrations of IFN-alpha were needed to turn on MxA (an antiviral gene) and MxB gene expression. The basal expression of IFN-alpha receptor (IFNAR1 and IF-NAR2) JAK1 and TYK2 mRNAs was readily detectable, and their expression was not significantly altered by treatment with either IFN-alpha or IFN-gamma. Hepatoma cells possessed relatively low basal expression levels of IFN signaling molecules STAT1, STAT2 and p48, but their expression was strongly upregulated by both types of IFNs. Pretreatment of HepG2 or HuH7 with low IFN-gamma doses, followed by stimulation with IFN-alpha, resulted in a marked enhancement of the formation of IFN-alpha-specific signaling complex ISGF3. CONCLUSION: The results indicate positive feedback mechanisms in the IFN signaling system in hepatoma cells.

Animals↗
PubMed2000

Clinical pathway of elderly persons with lowered mood in the health care services.

Elderly persons with mild depression are notable consumers of somatic health services. This study describes the typical clinical pathway including institutional care of two groups, depressed and non-depressed elderly persons, in different stages of the health care system, and compares possible changes in the use of health care services between the two groups. We also compare differences in morbidity and mortality between depressed and non-depressed persons. The depressed group of 50 persons in our follow-up study were selected randomly from among those persons who were diagnosed as having symptoms of depression, as shown in the Zung Self-Rating Depression Scale (n = 109). Persons (n = 50) who were not diagnosed as suffering from depression and who showed no signs of cognitive impairment (n = 833) were likewise chosen at random as a control group. We found that people suffering from symptoms of depression utilized institutional care, home health care and the outpatient clinics more than non-depressed people. Depressed people were more likely to suffer cardiovascular (p < 0.023) and pulmonary diseases (p < 0.04) than non-depressed controls. The mortality among depressed people was significantly higher than that in the control group. The results of our study give reason to believe that home-care staff are in a key position to identify depressed subjects. They have to understand the relationship between depression and the effect of various diseases on health and functional capacity. It is also important to ensure efficient communication between those responsible for health care.

Affect↗
PubMed1999

Interferon-alpha activates multiple STAT proteins and upregulates proliferation-associated IL-2Ralpha, c-myc, and pim-1 genes in human T cells.

Interferon-alpha (IFN-alpha) is a pleiotropic cytokine that has antiviral, antiproliferative, and immunoregulatory functions. There is increasing evidence that IFN-alpha has an important role in T-cell biology. We have analyzed the expression of IL-2Ralpha, c-myc, and pim-1 genes in anti-CD3-activated human T lymphocytes. The induction of these genes is associated with interleukin-2 (IL-2)-induced T-cell proliferation. Treatment of T lymphocytes with IFN-alpha, IL-2, IL-12, and IL-15 upregulated IL-2Ralpha, c-myc, and pim-1 gene expression. IFN-alpha also sensitized T cells to IL-2-induced proliferation, further suggesting that IFN-alpha may be involved in the regulation of T-cell mitogenesis. When we analyzed the nature of STAT proteins capable of binding to IL-2Ralpha, pim-1, and IRF-1 GAS elements after cytokine stimulation, we observed IFN-alpha-induced binding of STAT1, STAT3, and STAT4, but not STAT5 to all of these elements. Yet, IFN-alpha was able to activate binding of STAT5 to the high-affinity IFP53 GAS site. IFN-alpha enhanced tyrosine phosphorylation of STAT1, STAT3, STAT4, STAT5a, and STAT5b. IL-12 induced STAT4 and IL-2 and IL-15 induced STAT5 binding to the GAS elements. Taken together, our results suggest that IFN-alpha, IL-2, IL-12, and IL-15 have overlapping activities on human T cells. These findings thus emphasize the importance of IFN-alpha as a T-cell regulatory cytokine.

CD3 Complex↗
PubMed1999

Prevention of Type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study (DPS) in Finland. Study design and 1-year interim report on the feasibility of the lifestyle intervention programme.

UNLABELLED: AIMS/HYPOTHESIS; The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II (non-insulin-dependent) diabetes mellitus in subjects with impaired glucose tolerance, to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance. METHODS: A total of 523 overweight subjects with impaired glucose tolerance ascertained by two oral glucose tolerance tests were randomised to either a control or intervention group. The control subjects received general information at the start of the trial about the lifestyle changes necessary to prevent diabetes and about annual follow-up visits. The intervention subjects had seven sessions with a nutritionist during the first year and a visit every 3 months thereafter aimed at reducing weight, the intake of saturated fat and increasing the intake of dietary fibre. Intervention subjects were also guided individually to increase their physical activity. RESULTS: During the first year, weight loss in the first 212 study subjects was 4.7 +/- 5.5 vs 0.9 +/- 4.1 kg in the intervention and control group, respectively (p < 0.001). The plasma glucose concentrations (fasting: 5.9 +/- 0.7 vs 6.4 +/- 0.8 mmol/l, p < 0.001; and 2-h 7.8 +/- 1.8 vs 8.5 +/- 2.3 mmol/l, p < 0.05) were significantly lower in the intervention group after the first year of intervention. Favourable changes were also found in blood pressure, serum lipids and anthropometric indices in the intervention group. CONCLUSION/INTERPRETATION: The interim results show the efficacy and feasibility of the lifestyle intervention programme.

Blood Glucose↗
PubMed1999

Long-term effects of diltiazem and atenolol on blood glucose, serum lipids, and serum urate in hypertensive patients. Swedish-Finnish Study Group.

UNLABELLED: The purpose of this long-term treatment study was to evaluate health-related quality of life by comparing the effects of diltiazem and atenolol on some important metabolic parameters. SUBJECTS, MATERIAL AND METHODS: In a Swedish-Finnish long-term multicenter study 256 patients with mild to moderate hypertension were randomized to treatment with diltiazem retard (D) (n = 127) or atenolol (A) (n = 129). Doses could be increased and additional captopril medication be given to achieve adequate blood pressure (BP) reduction. The treatment in group D lasted for two years while group A was treated for 1 year and then was given D for another 2 years. RESULTS: After 1 year BP was significantly reduced in both groups and to a similar degree. The BP reduction was maintained during the rest of the study. After 1 and 2 years, HDL had increased significantly (p < 0.001) in group D. There was a corresponding significant reduction of the LDL/HDL ratio. In group A there were no changes after 1 year regarding lipoprotein levels. After the switch to D, group A showed similar improvements regarding HDL and the LDL/HDL ratio as the original D group. CONCLUSION: It is concluded that D and A are equally effective in lowering BP. However, long-term treatment with D, but not with A, has a favorable effect on HDL concentrations and the LDL/HDL ratio. According to these findings D affects the risk factor profile in hypertension.

Adult↗
PubMed1999

Coexistence of lowered mood and cognitive impairment of elderly people in five birth cohorts.

The prevalences of lowered mood and cognitive impairment, and their combination were investigated in 1993 random subjects of five birth cohorts (at age of 65, 70, 75, 80 and 85 years). The frequency of a high Zung-score (> 45), indicating depressive symptoms, in the five age groups was 11%, 13%, 20%, 16%, and 36%, respectively. The corresponding figures for a low MMSE-score (Mini Mental State Examination < 24) were 11%, 9%, 25%, 46%, and 60%; the respective frequencies of subjects fulfilling both criteria simultaneously were 2%, 3%, 8%, 12% and 24%, respectively. Overall, about 30% of the subjects with a low MMSE-score had a high Zung-score. However, more than half of the old subjects (over 75 years) with a high Zung-score also had low MMSE-scores. The data indicate that the combination of impaired cognition and lowered mood doubles in frequency by five-year intervals after the age of 70 years in the general aged population, and that this condition is present in one of four subjects at the age of 85 years.

Affect↗
PubMed1998

Inverse association of serum cholesterol with plasma insulin in the elderly. Cross-sectional and prospective analyses.

Cross-sectional studies have suggested that high plasma insulin is associated with relatively low levels of low density lipoprotein (LDL)-cholesterol. The present study was aimed at re-testing this association in a 70-year-old age cohort (N = 1023), and testing whether it could be caused by excessive mortality of hyperinsulinemic subjects with high LDL-cholesterol. A reverse U-shaped association between LDL-cholesterol and fasting plasma insulin was confirmed. LDL-cholesterol, HDL-cholesterol and total cholesterol were lowest in the highest insulin quarter. These associations remained after adjustment for diabetes, obesity and general health status. The combination of high LDL-cholesterol (> 4.25 mmol/L, 75th percentile) and high insulin (> 10 IU/L, 50th percentile) was not associated with excess 5-year mortality in this age cohort. Nor was it associated with excess mortality in four other elderly age cohorts (N = 1188), in which similar associations of cholesterol and insulin have been demonstrated. Thus, the inverse association of LDL-cholesterol with fasting insulin in the elderly is not caused by selective over mortality.

Aged↗
PubMed1998

The proximal interferon-stimulated response elements are essential for interferon responsiveness: a promoter analysis of the antiviral MxA gene.

Interferon (IFN)-inducible human MxA protein mediates resistance against influenza and several other RNA viruses. The MxA gene is under the control of type I IFN and, in certain cell types, is also directly activated by viruses. Here we show that in human macrophages, MxA mRNA levels are upregulated by very low doses of IFN-alpha in a dose-dependent manner. A similar, albeit much weaker, dose-dependent induction was seen with IFN-gamma. The induction was rapid and independent of protein synthesis. Interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) did not influence MxA mRNA levels alone or in combination with IFNs, in spite of the presence of putative response elements of these cytokines in the MxA promoter. We show that the promoter of the MxA gene contains two functional IFN-stimulated response elements (ISRE) near the transcription start site and one homologous ISRE-like element, which is apparently nonfunctional, further upstream. The two proximal ISRE sites are essential for IFN-alpha-induced transcription and appear to be binding sites for IFN-stimulated gene factor 3 complex. In addition, EMSA and DNAse I footprinting analysis demonstrated that Spl binds with high affinity to a region encompassing nucleotides -25 and -50 and, thus, may provide means of interaction with the basal transcriptional machinery.

Antiviral Agents↗
PubMed1998

Inverse correlation between serum testosterone and leptin in men.

Besides its role in the regulation of energy balance, leptin seems to be involved in linking energy stores to the reproductive system. A gender-dependent difference exists in plasma leptin concentration and leptin messenger ribonucleic acid expression in rodents and humans. This difference does not seem to be explained simply by differences in the amount of body fat between genders. To elucidate the relationship of endogenous testosterone and leptin, we studied the serum leptin concentrations in 269 elderly nondiabetic men. In addition, to assess whether exogenously administered testosterone could influence leptin production, we followed the serum levels of leptin in 10 healthy men during a 12-month treatment with 200 mg testosterone enanthate, i.m., weekly for contraceptive purposes. We found that the serum leptin concentration correlated inversely (r = -0.39; P < 0.001) with that of testosterone in elderly men. This inverse correlation was still present when body mass index and plasma insulin were included in the analysis. The administration of testosterone to young men suppressed serum leptin from the pretreatment level of 3.4 +/- 1.4 to 1.9 +/- 0.6 micrograms/L during the therapy. After cessation of testosterone injections, serum leptin concentration returned back to the pretreatment level. It is concluded that testosterone has a suppressive effect on leptin production, as reflected by circulating levels of this hormone.

Adult↗
PubMed1998

Regulation of IRF and STAT gene expression by retinoic acid.

Retinoic acid has antiproliferative and differentiative effects on many cell types. However, the molecular mechanisms involved in ATRA (all-trans retinoic acid) -dependent growth inhibition and cell differentiation are poorly understood. On the other hand, several different cytokine specific transcription factors such as signal transducers and activators of transcription (STAT) and interferon regulatory factors (IRF) are known to be instrumental in mediating differentiative, growth regulatory and antiproliferative effects in cells. The IRF family consists of six different proteins, of which IRF-1 has been demonstrated to have antiproliferative and tumor suppressive functions. We have shown that ATRA activates IRF-1 gene expression in several myeloid leukemia cell lines (HL-60, NB4, THP-1, U937), all of which respond to ATRA by growth inhibition. In addition, during ATRA-induced myeloid differentiation, gene expression of STAT1, STAT2, and p48 was upregulated. These proteins are involved in IFN-alpha specific signaling. ATRA-induced expression of IRF and/or STAT transcription factors may be one of the molecular mechanisms mediating growth inhibition by ATRA.

DNA-Binding Proteins↗