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Biomedical subjects

J Kuusisto

Publications and source records attributed to J Kuusisto.

At least 37 records · Page 2Linked to original sources
PubMed1999

Exopolysaccharide-producing bacteria from sugar beets.

Six hundred microorganisms were isolated from sugar beets collected from different parts of Finland to study their slime production. A total of 170 of them produced exopolysaccharides, of which 35% were heteropolysaccharides. The yield of heteropolysaccharides from sucrose was lower than that of dextrans. Five isolates, which were chosen for closer study, were identified as Leuconostoc mesenteroides (two species), Rahnella aquatilis (two species), and Enterobacter amnigenus.

Journal Article↗
PubMed1999

LDL size and risk of coronary heart disease in elderly men and women.

A predominance of small, dense, low density lipoprotein (LDL) particles has consistently been associated with coronary heart disease (CHD) in young and middle-aged subjects in cross-sectional studies. Recently, 3 prospective, case-control studies showed that decreased LDL size is a predictor of CHD in middle-aged subjects. However, it is not known whether decreased LDL size is mainly associated with premature CHD or whether it continues to play a role in CHD risk at older ages also. We performed a prospective, nested case-control study in 86 subjects (58 nondiabetic and 28 type 2 diabetic) aged 65 to 74 years who were free of myocardial infarction at baseline and who then had a myocardial infarction or CHD death during a 3.5-year follow-up (cases) and in 172 controls matched for sex and diabetes status but who remained free of CHD during follow-up. LDL particle size determined by gradient gel electrophoresis (268.2+/-0.9 versus 268.5+/-0.7 A, P=0.782) and the proportion of subjects with LDL subclass phenotype B (20.9 versus 21. 5, P=0.914) were similar among cases and controls. Furthermore, diastolic blood pressure, total cholesterol, high density lipoprotein cholesterol, triglycerides, apolipoprotein A(1), fasting glucose, fasting insulin, waist-to-hip ratio, and body mass index were not associated with CHD risk. However, smoking and increased systolic blood pressure, apolipoprotein B levels, and the total cholesterol-high density lipoprotein cholesterol ratio were significant predictors of CHD events both in univariate and multivariate analyses. Our findings indicate that LDL size is not a predictor of CHD events in elderly white subjects after controlling for diabetes status.

Aged↗
PubMed1998

The cardiac beta-myosin heavy chain gene is not the predominant gene for hypertrophic cardiomyopathy in the Finnish population.

OBJECTIVES: The aim of the study was to screen 36 unrelated patients with hypertrophic cardiomyopathy (HCM; 16 familial and 20 sporadic cases) from a genetically homogeneous area in eastern Finland for variants in the cardiac beta-myosin heavy chain (beta-MHC) and alpha-tropomyosin (alpha-TM) genes. BACKGROUND: Mutations in the beta-MHC and alpha-TM genes have been reported to be responsible for 30% to 40% and less than 5% of familial HCM cases, respectively. However, most genetic studies have included patients from tertiary care centers and are subject to referral bias. METHODS: Exons 3-26 and 40 of the beta-MHC gene and the nine exons of the alpha-TM gene were screened with the PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) method. Linkage analyses between familial HCM locus and two intragenic polymorphic markers (MYO I and MYO II) of the beta-MHC gene were performed in 16 familial HCM kindreds. RESULTS: A previously reported Arg719Trp (arginine converted to tryptophan in codon 719) mutation of the beta-MHC gene was found in one proband and two relatives. In addition, a novel Asn696Ser (asparagine converted to serine in codon 696) substitution was found in one HCM patient. No linkage between familial HCM and the beta-MHC gene was observed in 16 familial kindreds. A previously reported Aspl75Asn (aspartic acid converted to asparagine in codon 175) mutation of the alpha-TM gene was found in four probands and 16 relatives. Mutations in the beta-MHC and alpha-TM genes accounted for 6% and 25% familial HCM cases and 3% and 11% of all cases, respectively. CONCLUSIONS: Our results indicate that the beta-MHC gene is not the predominant gene for HCM in the Finnish population, whereas HCM caused by the Aspl75Asn mutation of the a-TM gene is more common than previously reported.

Amino Acid Substitution↗
PubMed1998

Can degenerative aortic valve stenosis be related to persistent Chlamydia pneumoniae infection?

BACKGROUND: The cause of age-related degenerative (tricuspid) aortic valve calcification is largely unknown, but one typical characteristic is an active inflammatory process. The presence of Chlamydia pneumoniae in aortic valve stenosis was recently shown. OBJECTIVE: To test the hypothesis that if persistent C. pneumoniae infection plays an active role in the development of aortic stenosis, the organism can be detected in the healthy aortic valves of young persons. DESIGN: A cadaver study. SETTING: Oulu University Hospital, Oulu, Finland. SUBJECTS: 46 consecutive cadavers undergoing autopsy. MEASUREMENTS: Macroscopic and histologic pathology of aortic valves was determined. The presence of C. pneumoniae was determined by immunohistochemistry. RESULTS: 34 of 46 valves were macroscopically normal. Early lesions of aortic valve disease were found in 12 valves (no lesions in valves from persons 20 to 40 years of age [n = 15], 4 lesions in valves from persons 41 to 60 years of age [n = 16], and 8 lesions in valves from persons older than 60 years of age [n = 15]; P = 0.004). Fifteen of 34 normal valves (44%) and 10 of 12 valves with early lesions (83%) had positive results on staining for C. pneumoniae (P = 0.02). In persons older than 60 years of age, the chance of an early lesion was higher if the valve tested positive for C. pneumoniae (7 of 8 valves with C. pneumoniae infection compared with 1 of 7 valves without C. pneumoniae infection; P = 0.01). CONCLUSIONS: Chlamydia pneumoniae is frequently present in aortic valves and is associated with early lesions of aortic valve stenosis in elderly persons.

Adult↗
PubMed1998

A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity.

The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription factor that has a pivotal role in adipocyte differentiation and expression of adipocyte-specific genes. The PPARgamma1 and gamma2 isoforms result from alternative splicing and have ligand-dependent and -independent activation domains. PPARgamma2 has an additional 28 amino acids at its amino terminus that renders its ligand-independent activation domain 5-10-fold more effective than that of PPARgamma1. Insulin stimulates the ligand-independent activation of PPARgamma1 and gamma2 (ref. 5), however, obesity and nutritional factors only influence the expression of PPARgamma2 in human adipocytes. Here, we report that a relatively common Pro12Ala substitution in PPARgamma2 is associated with lower body mass index (BMI; P=0.027; 0.015) and improved insulin sensitivity among middle-aged and elderly Finns. A significant odds ratio (4.35, P=0.028) for the association of the Pro/Pro genotype with type 2 diabetes was observed among Japanese Americans. The PPARgamma2 Ala allele showed decreased binding affinity to the cognate promoter element and reduced ability to transactivate responsive promoters. These findings suggest that the PPARgamma2 Pro12Ala variant may contribute to the observed variability in BMI and insulin sensitivity in the general population.

Adult↗
PubMed1998

Cognitive function in an elderly population with persistent impaired glucose tolerance.

OBJECTIVE: To study cognitive function in an elderly population with persistent impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Fasting and postload 2-h plasma glucose and insulin levels were determined at baseline in a population-based sample of 1,300 people and repeated an average of 3.5 years later in 980 subjects. At follow-up, cognitive function was evaluated in subjects with persistent normal glucose tolerance (NGT; n = 506) and IGT (n = 80) with a brief neuropsychological test battery. RESULTS: Subjects with persistent IGT scored lower in the Mini-Mental State Examination (MMSE) and in the Buschke Selective Reminding Test long-term memory scores. Multiple linear regression analysis revealed that age, education, and insulin levels (either fasting or 2-h value) were associated with the MMSE score in subjects with persistent IGT. Other potential risk factors for impaired cognitive function were not significantly associated with the MMSE score. CONCLUSIONS: Our study showed that persistent IGT in the elderly is associated with mildly impaired cognitive function, and hyperinsulinemia may account for this association.

Age Factors↗
PubMed1998

Glucokinase gene islet promoter region variant (G-->A) at nucleotide -30 is not associated with reduced insulin secretion in Finns.

OBJECTIVE: To investigate the effect of the islet promoter region variant (G-->A) at nucleotide -30 of the glucokinase (GCK) gene on insulin levels in subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and NIDDM. RESEARCH DESIGN AND METHODS: The study population included 294 subjects with NGT, 83 subjects with IGT, and 36 subjects with NIDDM. Oral glucose tolerance tests (OGTTs) were performed in all subjects, and intravenous glucose tolerance tests (IVGTTs) were performed in subjects with NGT. The islet promoter region of the GCK gene was amplified with polymerase chain reaction and screened for the variant (-30) using single-strand conformation polymorphism analysis. RESULTS: The islet promoter variant (-30) of the GCK gene was found in 17% of subjects with NGT, 23% of subjects with IGT, and 14% of patients with NIDDM (NS between the groups). Fasting, 1-h, and 2-h insulin levels, measured by OGTT, did not differ between subjects with and without this variant in any of the three groups. Furthermore, first-phase insulin secretion, determined by an IVGTT in subjects with NGT, did not associate with presence of the islet promoter region variant (-30) of the GCK gene. CONCLUSIONS: These results indicate that the variant (-30) of the islet promoter region of the GCK gene does not have a significant effect on insulin secretion in Finnish subjects with NGT, IGT, or NIDDM.

Administration, Oral↗
PubMed1997

Association between features of the insulin resistance syndrome and Alzheimer's disease independently of apolipoprotein E4 phenotype: cross sectional population based study.

OBJECTIVE: To determine the association between features of the insulin resistance syndrome and Alzheimer's disease. DESIGN: Cross sectional population based study. SUBJECTS: 980 people aged 69 to 78 (349 men, 631 women). SETTING: Population of Kuopio, eastern Finland. MAIN OUTCOME MEASURES: Presence of features of the insulin resistance syndrome and diagnosis of Alzheimer's disease by detailed neurological and neuropsychological evaluation. RESULTS: 46 (4.7%) subjects were classified as having probable or possible Alzheimer's disease. In univariate analyses, apolipoprotein E4 phenotype (odds ratio; 95% confidence interval 3.24: 1.77 to 5.92), age (1.16; 1.05 to 1.29), low level of education (0.82; 0.72 to 0.93), low total cholesterol concentration (0.77; 0.59 to 1.00), high systolic blood pressure (1.01; 1.00 to 1.03), high fasting and 2 hour plasma glucose concentrations (1.11; 1.01 to 1.23 and 1.08; 1.03 to 1.13, respectively), high fasting and 2 hour insulin concentrations (1.05; 1.02 to 1.08 and 1.003; 1.00 to 1.01, respectively), and abnormal glucose tolerance (1.86; 1.23 to 2.80) were significantly associated with Alzheimer's disease. In multivariate analysis including apolipoprotein E4 phenotype, age, education, systolic blood pressure, total cholesterol concentration, fasting glucose concentration, and insulin concentration, apolipoprotein E4 phenotype, age, education, total cholesterol, and insulin were significantly associated with Alzheimer's disease. In 532 non-diabetic subjects without the e4 allele hyperinsulinaemia was associated with an increased risk for Alzheimer's disease (prevalence of disease 7.5% v 1.4% in normoinsulinaemic subjects, P = 0.0004). In contrast, in the 228 with the e4 allele hyperinsulinaemia had no effect on the risk of disease (7.0% v 7.1%, respectively). CONCLUSION: Features of the insulin resistance syndrome are associated with Alzheimer's disease independently of apolipoprotein E4 phenotype.

Aged↗
PubMed1997

New variants in the glycogen synthase gene (Gln71His, Met416Val) in patients with NIDDM from eastern Finland.

Impaired glycogen synthesis after insulin stimulation accounts for most of the insulin resistance in patients with non-insulin-dependent diabetes mellitus (NIDDM). The glycogen synthase gene (GYS1), which encodes the rate-limiting enzyme for glycogen synthesis, is a promising candidate gene for NIDDM. Therefore, we screened all 16 exons of this gene by single-strand conformation polymorphism analysis in 40 patients with NIDDM (age 67 +/- 2 years, body mass index 28.2 +/- 0.6 kg/m2) from Taipalsaari, eastern Finland. The Gly464Ser variant (exon 11) and a silent polymorphism TTC342TTT (exon 7) have been reported previously. In addition, we found a new variant Gln71His (exon 2) and a new amino acid polymorphism Met416Val (exon 10). An additional sample of 65 patients with NIDDM and 82 normoglycaemic men (age 54 +/- 1 years, body mass index 26.3 +/- 1.4 kg/m2) were screened. The allele frequency of the TTC342TTT silent substitution was 0.29 in both NIDDM and normoglycaemic subjects. The Gln71His and Gly464Ser variants were found in 1 (1%) and 3 (3%) subjects, respectively, of the 105 NIDDM patients and in none of the 82 normoglycaemic men. The Met416Val polymorphism was found in 16 (15%) of the 105 NIDDM patients and in 14 (17%) of the 82 control subjects (all heterozygous). The Met416Val polymorphism was not associated with insulin resistance in two groups of normoglycaemic subjects. In conclusion, the new Gln71His and Met416Val substitutions and other variants of the glycogen synthase gene are unlikely to make a major contribution to insulin resistance and NIDDM in diabetic patients from eastern Finland.

Aged↗
PubMed1997

Detection of Chlamydia pneumoniae in human nonrheumatic stenotic aortic valves.

OBJECTIVES: We sought to study the possible presence of Chlamydia pneumoniae in aortic valve stenosis (AVS). BACKGROUND: Inflammation and immune mechanisms are considered important for the pathogenesis of nonrheumatic AVS. All chlamydial species are able to cause heart infections, and seroepidemiologic studies have indicated an association between chronic C. pneumoniae infection and coronary artery disease. Furthermore, the organism has been demonstrated in atherosclerotic lesions. METHODS: Aortic valve specimens with varying degrees of macroscopic disease were obtained from 35 subjects--17 consecutive patients undergoing aortic valve replacement for treatment of nonrheumatic AVS and 18 age-matched subjects at autopsy. The possible presence of C. pneumoniae in aortic valves was studied by immunohistochemical analysis, polymerase chain reaction or transmission electron microscopy, or a combination of these. RESULTS: Positive immunohistochemical staining with C. pneumoniae specific antibody was found in 9 (53%) of 17 patients with advanced aortic valve disease requiring surgical treatment (group A), 8 (80%) of 10 cadavers with clearly macroscopic aortic valve pathology (group B) and 1 (12%) of 8 grossly normal cadaver control subjects (group C). Statistical significance with regard to the presence of C. pneumoniae was found when combined diseased subjects (groups A and B: total 17 of 27 subjects) were compared with group C (p = 0.018). However, when group A was compared with group C, there was only marginal statistical significance (p = 0.088). Finally, there was a strong statistical significance (p = 0.015) when groups B and C were compared. Chlamydia pneumoniae DNA was also found in three stenotic valves, and in two of the three tested valve specimens chlamydia-like particles were seen by electron microscopy. CONCLUSIONS: Chlamydia pneumoniae is frequently present in nonrheumatic AVS. Similarly, the high number of C. pneumoniae infections detected in the early lesions of "degenerative" AVS suggest that this pathogen may play an etiologic role in the development of this disease. The validity of this relation requires additional study.

Aged↗
PubMed1997

The Trp64Arg polymorphism of the beta 3-Adrenergic receptor gene. Lack of association with NIDDM and features of insulin resistance syndrome.

OBJECTIVE: To investigate the association of the Trp64Arg polymorphism of the beta3-adrenergic receptor gene with NIDDM and the features of insulin resistance syndrome in subjects from eastern Finland. RESEARCH DESIGN AND METHODS: We determined the prevalence of the Trp64Arg polymorphism of the beta3-adrenergic receptor gene by restriction fragment length polymorphism analysis in 110 patients with NIDDM (54 men and 56 women, age 63 +/- 1 years, BMI 30.4 +/- 0.5 kg/m2), in 183 patients with features of insulin resistance syndrome (103 men and 80 women, age 44 +/- 0 years, BMI 31.1 +/- 0.4 kb/m2), and in 82 normoglycemic control men (age 54 +/- 1 years, BMI 26.3 +/- 0.4 kg/m2). RESULTS: The allele frequency of the Trp64Arg polymorphism of the beta3-adrenergic receptor gene was similar in patients with NIDDM, in patients with insulin resistance syndrome, and in control subjects (0.08, 0.07, and 0.07, respectively; NS). In addition, this polymorphism was not associated with low resting metabolic rate, abdominal obesity, increased lipid oxidation, hypertension, or earlier development of NIDDM as previously described. Furthermore, in 82 normoglycemic male control subjects the Trp64Arg polymorphism was not associated with insulin resistance evaluated by the euglycemic-hyperinsulinemic clamp. CONCLUSIONS: The Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is unlikely to be a major genetic predisposer to NIDDM or insulin resistance syndrome in subjects from eastern Finland.

Adult↗
PubMed1996

Memory functions in human subjects with different apolipoprotein E phenotypes during a 3-year population-based follow-up study.

The apolipoprotein E epsilon4 allele is the most common risk factor for Alzheimer's disease (AD). The epsilon2 allele may play a protective role in AD. Our previous cross-sectional study showed that in non-demented elderly subjects the epsilon2 allele is associated with better learning ability than other alleles. We wished to investigate the influence of different apolipoprotein E (apoE) phenotypes on cognitive functions in a 3-year follow-up study starting with a random sample of 917 non demented elderly subjects. Episodic memory was examined with the List Learning Test (Buschke's selective reminding method), as well as with immediate and delayed recall of figures. Retrieval from semantic memory was assessed with the Category and Verbal Fluency tests. Constructional abilities were examined by copying figures. Attention functions were examined with the Trail Making A and B tests. A total of 632 subjects completed the 3-year follow-up study. The subjects with apoE phenotypes E2/2 or E2/3 were able to maintain their verbal learning performance, while the learning ability of the subjects with other apoE phenotypes deteriorated. We suggest that successful mental aging may be at least in part associated with genetic factors.

Aged↗
PubMed1996

Gender differences in left ventricular function at rest and with exercise in asymptomatic aortic stenosis.

In 29 women and 53 men with asymptomatic aortic stenosis, two-dimensional (2-D) and Doppler echocardiography were performed at rest and immediately after treadmill exercise testing to examine gender differences in left ventricular geometry, systolic and diastolic function, functional status, and exercise capacity. Aortic stenosis severity was similar between men and women. Women reported more functional impairment than men (88% +/- 14% vs 95% +/- 7%; p = 0.02). When indexed to body surface area, women had a smaller end-diastolic volume (39 +/- 14 vs 50 +/- 15 ml/m2; p = 0.002), end-systolic volume (13 +/- 6 ml/m2 vs 18 +/- 9 ml/m2; p = 0.01) and left ventricular mass (73 +/- 26 gm/m2 vs 84 +/- 21 gm/m2; p = 0.05), but a higher relative wall thickness in systole (1.5 +/- 0.4 cm vs 1.3 +/- 0.4 cm; p = 0.05), and fractional shortening (43% +/- 7% vs 39% +/- 10%; p = 0.03). Women had higher early and late transmitral velocities than did men (early, 92 +/- 24 cm/sec vs 79 +/- 29 cm/sec; p = 0.05; late, 97 +/- 30 cm/sec vs 68 +/- 23 cm/sec; p < 0.0001), a higher time-velocity integral in early diastole (18.2 +/- 4.8 cm vs 15.1 +/- 4.3 cm; p = 0.006), a significantly shorter exercise duration (4.5 +/- 4.1 minutes vs 8.0 +/- 3.9 minutes; p < 0.0001), a greater degree of functional aerobic impairment (25% +/- 48% vs 2% +/- 33%; p = 0.02), and a smaller increase in cardiac output with exercise (5.4 +/- 3.5 L/min vs 8.0 +/- 4.3 L/min; p = 0.01), in spite of similar peak heart rate and blood pressure responses. In these asymptomatic subjects with aortic stenosis, women had smaller, relatively hypercontractile ventricles, a different diastolic filling profile, more exercise limitation, and poorer functional capacity. These findings demonstrate the importance of gender in the response of the left ventricle to chronic pressure overload.

Adult↗
PubMed1996

Apolipoproteins B, (a), and E accumulate in the morphologically early lesion of 'degenerative' valvular aortic stenosis.

Nonrheumatic aortic stenosis of trileaflet aortic valves has been considered to be a "degenerative" process, but the early lesion of aortic stenosis contains the chronic inflammatory cells, macrophages and T lymphocytes. Because lipoprotein deposition is prominent in atherosclerosis, another chronic inflammatory process, this study examined whether lipoproteins accumulate in aortic valve lesions. Immunohistochemical studies were performed to detect apolipoprotein (apo) B, apo(a), apoE, macrophages, and alpha-actin-expressing cells on 18 trileaflet aortic valves that ranged from normal to stenotic. All three apolipoproteins were detected in early through end-stage lesions of aortic stenosis but not in histologically normal regions. Comparison with oil red O staining suggested that most of the extracellular neutral lipid in these valves was associated with either plasma-derived or locally produced apolipoproteins. Thus, in early through end-stage aortic valve lesions, apolipoproteins accumulate and are associated with the majority of extracellular valve lipid. These results are consistent with the hypothesis that lipoprotein accumulation in the aortic valve contributes to pathogenesis of aortic stenosis.

Aortic Valve↗