Search PubMed⌕ Search

Biomedical subjects

J Heikkinen

Publications and source records attributed to J Heikkinen.

At least 55 records · Page 3Linked to original sources
PubMed1995

Iodine-123 labelled N-(2-fluoroethyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane for dopamine transporter imaging in the living human brain.

There are several cocaine analogs which have potential for imaging the dopamine transporters (DAT). Earlier studies have shown that iodine-123 labelled 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane ([123I]beta-CIT) and N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane ([123I]beta-CIT-FP) are promising DAT imaging agents in the living human brain with single-photon emission tomography (SPET). Here we report a pilot comparison of [123I]beta-CIT and [123I]beta-CIT-FP with a new tropane derivative, [123I]N-(2-fluoroethyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane ([123I]beta-CIT-FE), using SPET imaging in four healthy male subjects. Peak uptake of [123I]beta-CIT-FE into the basal ganglia occurred very rapidly (0.5 h after injection of tracer), after which the striatal washout obeyed a bi-exponential form. The specific DAT binding of [123I]beta-CIT-FE into the basal ganglia was somewhat less (0.785 +/- 0.117) than that of [123I]beta-CIT (0.922 +/- 0.004) or [123I]beta-CIT-FP (0.813 +/- 0.047). All these tracers have excellent imaging quality in healthy control subjects. However, the relatively fast washout of [123I]beta-CIT-FE and low temporal resolution of older SPET cameras may limit the use of this tracer to the measurement of the DAT density.

Adult↗
PubMed1995

Can progestin be limited to every third month only in postmenopausal women taking estrogen?

We evaluated whether a progestin, added for 14 days every 3 months to estrogen replacement therapy, is capable of preventing the development of endometrial hyperplasia in postmenopausal women during a treatment period of 2 years. Postmenopausal women (263) in 10 hospitals and medical centers in Finland participated in this non-randomized prospective multicenter trial. The women received estradiol valerate 2 mg daily for 84 days and 20 mg of medroxyprogesterone acetate daily for days 71-84 followed by seven drug-free tablets. This regimen was repeated four times per year. The first year of treatment was completed by 227 (86%) women and the second year by 143 out of 146 women. The incidence of unscheduled and heavy bleedings was higher in women who were postmenopausal for less than 3 years. Endometrial biopsies demonstrated progestational response in 64% at 12 and 24 months, respectively. The 3 month regimen prevented development of endometrial hyperplasia but was not able to restore a hyperplastic endometrium to normal.

Adult↗
PubMed1994

Lysyl hydroxylase, a collagen processing enzyme, exemplifies a novel class of luminally-oriented peripheral membrane proteins in the endoplasmic reticulum.

Lysyl hydroxylase (LH), an enzyme required early during collagen biosynthesis, appears to be exceptional among proteins that are thought to be residents of the endoplasmic reticulum (ER). It is a homodimer and does not contain either of the two previously characterized ER-specific retention motifs (KDEL or the double lysine motif) in its primary structure. We now show that LH, nevertheless, resides in the lumen of the ER. In immunofluorescence experiments, LH co-localizes with a KDEL-containing protein, protein disulfide isomerase (PDI), and also co-sediments with it after fractionation of subcellular organelles by sucrose density gradient centrifugation. In addition, LH seems to be stress-inducible. In one respect, however, LH differs from PDI and other known luminal proteins in the organelle. It is found in situ only in association with the ER membranes. Our cell fractionation and Triton X-114 phase separation experiments suggest that it binds to the membranes via weak electrostatic interactions. LH can thus be regarded as a first luminally-oriented "peripheral membrane" protein which has been characterized in the ER. The results suggest a novel possibility by which ER lumen can acquire its specific protein components from the bulk flow.

Amino Acid Sequence↗
PubMed1994

Exercise, smoking, and calcium intake during adolescence and early adulthood as determinants of peak bone mass. Cardiovascular Risk in Young Finns Study Group.

OBJECTIVE: To evaluate the contribution to peak bone mass of exercise, smoking, and calcium intake in adolescents and young adults. DESIGN: Prospective cohort study with end point measurement (bone mineral density) after 11 years' follow up for lifestyle. SETTING: Five university hospital clinics. SUBJECTS: 264 (153 females, 111 males) subjects aged 9 to 18 years at the beginning of the follow up and 20 to 29 years at the time of measurement of bone mineral density. MAIN OUTCOME MEASURE: Bone mineral density of lumbar spine and femoral neck by dual energy x ray absorptiometry; measures of physical activity and smoking and estimates of calcium intake repeated three times during follow up. RESULTS: In the groups with the lowest and highest levels of exercise the femoral bone mineral densities (adjusted for age and weight) were 0.918 and 0.988 g/cm2 for women (P = 0.015, analysis of covariance) and 0.943 and 1.042 g/cm2 for men (P = 0.005), respectively; at the lumbar spine the respective values were 1.045 and 1.131 (P = 0.005) for men. In men the femoral bone mineral densities (adjusted for age, weight, and exercise) were 1.022 and 0.923 g/cm2 for the groups with the lowest and highest values of smoking index (P = 0.054, analysis of covariance). In women the adjusted femoral bone mineral density increased by 4.7% together with increasing calcium intake (P = 0.089, analysis of covariance). In multiple regression analysis on bone mineral density of the femoral neck, weight, exercise, age, and smoking were independent predictors for men; with weight, exercise, and age for women. These predictors together explained 38% of the variance in bone mineral density in women and 46% in men. At the lumbar spine, weight, smoking, and exercise were predictors for men; and only weight for women. CONCLUSIONS: Regular exercise and not smoking is important in achieving maximal peak bone mass in adolescents and young adults.

Absorptiometry, Photon↗
PubMed1994

Structure and expression of the human lysyl hydroxylase gene (PLOD): introns 9 and 16 contain Alu sequences at the sites of recombination in Ehlers-Danlos syndrome type VI patients.

Lysyl hydroxylase (EC 1.14.11.4) catalyzes the formation of hydroxylysine in collagens by the hydroxylation of lysine residues in peptide linkages. This enzyme activity is known to be reduced in patients with the type VI variant of the Ehlers-Danlos syndrome, and the first mutations in the lysyl hydroxylase gene (PLOD) have recently been identified. We have now isolated genomic clones for human lysyl hydroxylase and determined the complete structure of the gene, which contains 19 exons and a 5' flanking region with characteristics shared by housekeeping genes. The constitutive expression of the gene in different tissues further suggests that lysyl hydroxylase has an essential function. We have sequenced the introns of the gene in the region where many mutations and rearrangements analyzed to date are concentrated. Intron 9 and intron 16 show extensive homology resulting from the many Alu sequences found in these introns. Intron 9 contains five and intron 16 eight Alu sequences. The high homology and many short identical or complementary sequences in these introns generate many potential recombination sites with the gene. The delineation of the structure of the lysyl hydroxylase gene contributes significantly to our understanding of the rearrangements in the genome of Ehlers-Danlos type VI patients.

Amino Acid Sequence↗
PubMed1994

Apolipoprotein E and B polymorphisms--longevity factors assessed in nonagenarians.

To test if the prevalence of genetic risk factors for coronary heart disease (CHD) is low in individuals who have reached an extremely old age, the allele frequencies of apolipoprotein E (apo E) and B (apo B) polymorphisms and plasma lipoprotein(a) levels were investigated in nonagenarians and in younger control groups. The frequency of the epsilon 4 allele of apo E was significantly lower in the nonagenarians than in the middle-aged and young adults (P < 0.05). Also, the frequency of EcoRI allele R- of apo B was low in the nonagenarians, whereas the allele frequency for the XbaI polymorphism of apo B and plasma lipoprotein(a) concentrations did not differ between the nonagenarians and the younger groups. These findings strongly suggest that the presence of these potential genetic risk factors for CHD, namely the epsilon 4 allele of apo E and the R- allele of apo B, decreases the probability of an individual reaching an extremely old age.

Adult↗
PubMed1994

A Finnish multicentre quality assurance project in bone scintigraphy and brain SPET: a phantom study.

We examined all routinely used bone scintigraphy and brain single photon emission tomographic (SPET) systems in 19 laboratories in Finland. Physical performance of bone scintigraphy systems was measured with a 57Co flood source and with a NEMA resolution phantom. Total performance of the systems was evaluated with a transmission phantom simulating bone imaging of the thorax. It was acquired both with the protocol used in a given laboratory and with a fixed protocol. The participant laboratories were asked to report all accumulations on a diagrammatic thorax drawing. Tomographic uniformity, contrast and resolution (i.e. physical performance) of the SPET systems were evaluated with a special phantom. In addition, a Hoffman brain phantom was measured with routinely used acquiring and reconstruction protocols (total performance). All measurements were performed with the same test objects supervised by the same physicist. Manufacturer, age or the collimator of the camera did not correlate with the physical performance of the imaging systems (r < 0.65). This is probably due to lack of regular quality control of the gamma cameras in some laboratories. Comparison of the physical and the total performance shows that the detector itself is not necessarily responsible for inaccurate findings from the test object. Use of dual intensity and digital images in both scintigraphy could certainly increase the sensitivity of the findings: sensitivity of single intensity images was 65% (33-89%), dual 73% (28-100%), analog 65% (28-100%) and digital 74% (50-94%). Standardization of acquisition and reconstruction protocols will improve quality of brain SPET images and comparability between laboratories. This study showed the need for objective audit tests of bone scintigraphy and brain SPET systems in Finland.

Bone and Bones↗
PubMed1994

Alu-Alu recombination results in a duplication of seven exons in the lysyl hydroxylase gene in a patient with the type VI variant of Ehlers-Danlos syndrome.

The type VI variant of the Ehlers-Danlos syndrome (EDS) is a recessively inherited connective-tissue disorder. The characteristic features of the variant are muscular hypotonia, kyphoscoliosis, ocular manifestations, joint hypermobility, skin fragility and hyperextensibility, and other signs of connective-tissue involvement. The biochemical defect in most but not all patients is a deficiency in lysyl hydroxylase activity. Lysyl hydroxylase is an enzyme that catalyzes the formation of hydroxylysine in collagens and other proteins with collagen-like amino acid sequences. We have recently reported an apparently homozygous large-duplication rearrangement in the gene for lysyl hydroxylase, leading to the type VI variant of EDS in two siblings. We now report an identical, apparently homozygous large duplication in an unrelated 49-year-old female originally analyzed by Sussman et al. Our simple-sequence-repeat-polymorphism analysis does not support uniparental isodisomy inheritance for either of the two duplications. Furthermore, we indicate in this study that the duplication in the lysyl hydroxylase gene is caused by an Alu-Alu recombination in both families. Cloning of the junction fragment of the duplication has allowed synthesis of appropriate primers for rapid screening for this rearrangement in other families with the type VI variant of EDS.

Base Sequence↗
PubMed1993

A large duplication in the gene for lysyl hydroxylase accounts for the type VI variant of Ehlers-Danlos syndrome in two siblings.

Ehlers-Danlos syndrome is a heterogeneous disorder characterized by joint hypermobility, skin hyperextensibility, fragility, and other signs of connective tissue involvement. In addition to these, the type VI variant of the disease has some special characteristics such as kyphoscoliosis and ocular abnormalities. The biochemical abnormality in most patients with this autosomal recessively inherited type VI variant is a deficiency in the activity of lysyl hydroxylase (EC 1.14.11.4), the enzyme catalyzing the formation of hydroxylysine in collagens and other proteins with collagen-like amino acid sequences. The type VI variant of Ehlers-Danlos syndrome was first identified in two sisters with a reduced amount of lysyl hydroxylase activity in their skin fibroblasts (S.R. Pinnell, S. M. Krane, J. E. Kenzora, and M. J. Glimcher (1972) N. Engl. J. Med. 286: 1013-1020). Our recent molecular cloning of lysyl hydroxylase has now made it possible to study the mutations leading to the deficiency in lysyl hydroxylase activity in these cells. Our data indicate that the mRNA for lysyl hydroxylase produced in the affected cells is about 4 kb in size, whereas it is 3.2 kb in the control cells. The sequencing of the cDNA for lysyl hydroxylase from the affected cells revealed an apparently homozygous duplication rearrangement of nucleotides 1176 to 1955, corresponding to amino acids 326 to 585 in the normal sequence. From Southern blotting data, the duplicated area in the gene equals about 6-9 kb and corresponds to seven exons.

Amino Acid Sequence↗
PubMed1992

Minoxidil specifically decreases the expression of lysine hydroxylase in cultured human skin fibroblasts.

The levels of lysine hydroxylase protein and the levels of the mRNAs for lysine hydroxylase and the alpha- and beta-subunits of proline 4-hydroxylase were measured in cultured human skin fibroblasts treated with 1 mM-minoxidil. The data demonstrate that minoxidil decreases the amount of lysine hydroxylase protein, this being due to a decrease in the level of lysine hydroxylase mRNA. The effect of minoxidil appears to be highly specific, as no changes were observed in the amounts of mRNAs for the alpha- and beta-subunits of proline 4-hydroxylase.

Blotting, Northern↗
PubMed1992

Dual-energy X-ray absorptiometry in normal women: a cross-sectional study of 717 Finnish volunteers.

The bone mineral density (BMD) of the lumbar spine and proximal femur was measured using dual-energy X-ray absorptiometry in 717 healthy women aged 20-70 years. The maximal mean BMD was found at the age of 35-39 years in the spine and at the age of 20-24 in the femoral neck and Ward's triangle. No significant change in lumbar BMD was found from the age of 20 to 39 years. The spinal BMD values were relatively stable from age 20 to 39 years, whereas a linear decrease in BMD in the femoral neck and Ward's triangle was already apparent in the youngest age group (20-24 years). The major fall in BMD in all sites was related to the menopause. The overall decreases in BMD from the peak values to those at age 65-70 years were 20.4%, 19.0% and 32.6% in the lumbar spine, femoral neck and Ward's triangle, respectively. The correlation of trochanteric BMD with age was poor. BMD was positively correlated with weight in all measurement sites. Nulliparity was found to be a risk factor for osteoporosis. The present study confirmed that the menopause has a significant effect not only on spinal BMD but also on femoral BMD. Lumbar BMD was lower and BMDs in the proximal femur were higher in Finnish women than in white American women. This emphasizes the importance of national reference values for BMD measurements.

Absorptiometry, Photon↗
PubMed1991

Elevated high-density-lipoprotein cholesterol and normal triglycerides as markers of longevity.

Serum cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides of 85 year old home-living persons were compared to those of controls and of patients who had severe coronary artery disease (CAD) at an early age. Eighty-five-year-olds had higher serum HDL cholesterol than controls and patients with CAD. Patients with severe CAD had higher serum total cholesterol and serum triglycerides and lower HDL-cholesterol than other groups. When 85-year-old persons were divided into quintiles according to serum HDL cholesterol, women with highest HDL cholesterol had lowest mortality, men with lowest HDL cholesterol had highest mortality. We conclude that elevated HDL cholesterol is correlating with longevity and low HDL cholesterol with CAD at an early age.

Aged↗
PubMed1991

Moderate exercise does not enhance the positive effect of estrogen on bone mineral density in postmenopausal women.

We studied the effects of physical activity and two types of estrogen treatment in a prospective study in 78 healthy postmenopausal women. A control group and two treatment groups receiving estradiol valerate and medroxyprogesterone acetate in 1- or 3-month cycles were monitored for 1 year. Half of each group took part in an exercise program. Lumbar and femoral bone mineral density increased in both of the estrogen-treatment groups. Physical exercise with estrogen treatment did not result in further increases in bone mineral densities.

Bone Density↗
PubMed1991

Once daily compared with twice daily administration of slow-release diltiazem as monotherapy for hypertension.

We compared the efficacy of the antihypertensive drug diltiazem in a slow release formulation administered once daily with its twice daily administration as monotherapy in 34 patients with mild to moderate essential hypertension. All subjects received placebo for three weeks before the randomised, double blind, crossover study, and their supine diastolic blood pressure (BP) ranged from 95 mmHg to 115 mmHg. After the patients had received the placebo for three weeks diltiazem was titrated in the open label treatment to either 120 mg or 180 mg twice daily until the target BP level was achieved. After the open three weeks' of treatment with diltiazem twice daily patients were allocated randomly for either once daily or twice daily administration. After a six week, double blind period, the treatment was changed according to the crossover design. With a dose of 120 mg or 180 mg twice daily patients' supine and standing BP readings were significantly lower than when they took the drug once daily. In the subgroup (n = 19) with the maximum dose of diltiazem given twice daily and once daily BP levels were lower in those subjects on twice daily treatment than in those treated once a day with the same total daily dose, the differences being significant. Administration of diltiazem once a day in a slow release formulation was not as effective as a twice daily dose when the dose titration was greatest or when compared with the same dosage (240 mg x 1/day or 120 mg x 2/day).

Adult↗
PubMed1990

High-density lipoprotein cholesterol and longevity.

Serum total cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides were studied in three groups: (1) 85 healthy subjects aged 85-89 years, (2) 62 patients without coronary artery disease aged 38-62 years, and (3) 323 patients aged 32-69 years with triple-vessel disease diagnosed by coronary angiography. The mean values for total cholesterol were significantly higher in patients with triple-vessel disease than in those without coronary artery disease and in the elderly. Total cholesterol was over 6.5 mmol/l in 32% of the elderly, in 31% of patients without coronary artery disease and in 42% of patients with triple-vessel disease, but these differences were not significant. HDL-cholesterol and the ratio of HDL/total cholesterol were significantly higher in the elderly than in the patients without coronary artery disease and patients with triple-vessel disease. Serum HDL-cholesterol was over 1.0 mmol/l in 92% of the elderly, in 69% of patients without coronary artery disease and in 46% of patients with triple-vessel disease, the differences being significant between all groups.

Adult↗
PubMed1990

Serum cholesterol, high-density lipoprotein cholesterol and five-year survival in elderly people.

In the year 1982 serum cholesterol and high-density lipoprotein (HDL) cholesterol were measured in 535 people aged 85 years participating in a health survey screening. All subjects were living at home. During the 5-year follow-up, 186 (34.8%) of the subjects died. There was a J-shaped relation between serum cholesterol and mortality. Mortality was lowest at serum cholesterol 5.0-5.9 mmol/l for men and 7.0-7.9 mmol/l for women. The greatest mortality was observed in men with cholesterol greater than or equal to 6.0 mmol/l and in women with cholesterol greater than or equal to 8.0 mmol/l. There was a significant negative association of serum HDL cholesterol with mortality. Mortality was highest (53.3%) in men with serum HDL cholesterol less than 0.80 mmol/l. Mortality was low (16.5%) in women with serum HDL cholesterol greater than 1.8 mmol/l.

Aged↗