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Biomedical subjects

M Koskinen

Publications and source records attributed to M Koskinen.

At least 19 recordsLinked to original sources
PubMed2005

DNA repair and cyclin D1 polymorphisms and styrene-induced genotoxicity and immunotoxicity.

1-SO-adenine DNA adducts, DNA single-strand breaks (SBs), chromosomal aberrations (CAs), mutant frequency (MF) at the HPRT gene, and immune parameters (hematological and of humoral immunity) were studied in styrene-exposed human subjects and controls. Results were correlated with genetic polymorphisms in DNA repair genes (XPD, exon 23, XPG, exon 15, XPC, exon 15, XRCC1, exon 10, XRCC3, exon 7) and cell cycle gene cyclin D1. Results for biomarkers of genotoxicity after stratification for the different DNA repair genetic polymorphisms showed that the polymorphism in exon 23 of the XPD gene modulates levels of chromosomal and DNA damage, HPRT MF, and moderately affects DNA adduct levels. The highest levels of biomarkers were associated with the wild-type homozygous AA genotype. The exposed individuals with the wild-type GG genotype for XRCC1 gene exhibited the lowest CA frequencies, compared to those with an A allele (P < 0.05). Cyclin D1 polymorphism seems to modulate the number of leukocytes and lymphocytes in the analyzed subjects. The number of eosinophiles was positively associated with XPD variant C allele and negatively with XRCC1 variant A allele (P < 0.05) and XPC variant C allele (P < 0.05). Immunoglobulin IgA was positively associated with an XRCC3 variant T allele (P < 0.01) and negatively with XPC variant C allele (P < 0.05). Both C3- and C4-complement components were lower in individuals with XRCC3 CT (P < 0.05) and TT genotypes (P < 0.01). Adhesion molecules sL-selectin and sICAM-1 were associated with XPC genotype (P < 0.05). Individual susceptibility may be reflected in genotoxic and immunotoxic responses to environmental and occupational exposures to xenobiotics.

Adult↗
PubMed2005

Electron-hole duality and vortex rings in quantum dots.

In a quantum-mechanical system, particle-hole duality implies that instead of studying particles, we can get equivalent information by studying the missing particles, the so-called holes. Using this duality picture for fermions in a rotating trap the vortices appear as holes in the Fermi sea. Here we predict that the formation of vortices in quantum dots at high magnetic fields causes oscillations in the energy spectrum which can be experimentally observed using accurate tunneling spectroscopy. We use the duality picture to show that these oscillations are caused by the localization of vortices in rings.

Journal Article↗
PubMed2004

Universal vortex formation in rotating traps with bosons and fermions.

We show that the rotation of trapped quantum mechanical particles with a repulsive interaction can lead to vortex formation, irrespective of whether the particles are bosons or (unpaired) fermions. The exact many-particle wave function constitutes similar structures in both cases, implying that this vortex formation is indeed universal.

Journal Article↗
PubMed2004

A novel frozen brain tissue array technique: immunohistochemical detection of neuronal paraneoplastic autoantibodies.

We introduce a modification of the tissue microarray technique in which several frozen brain tissue specimens are collected to a single frozen brain array block. In the present application, we use it for the detection of neuronal paraneoplastic anti-Hu autoantibodies. Representative samples from 15 different brain regions were collected according to a standard neuropathological autopsy protocol. Cryostat sections from each block were cut and conventionally stained. From representative areas, cylinder tissue samples from each specimen were punched and then arrayed into a recipient array block. Using the cryostat sections of this brain array, autoantibodies from seven anti-Hu-positive patient sera (confirmed by immunoblotting) were screened by immunohistochemistry. Neuronal architecture was well preserved and immunohistochemical staining was comparable to that of conventional cryostat sections. Because of the variable staining pattern in different brain areas, two anti-Hu-positive sera could be detected immunohistochemically by the one brain array. With the present array technique, it is possible to characterize the variable staining patterns of neuronal paraneoplastic autoantibodies in different locations of the human brain. The frozen brain array also allows the detection of RNA and DNA targets involved in neurological diseases.

Aged↗
PubMed2004

Evoked EEG patterns during burst suppression with propofol.

BACKGROUND: During EEG suppression with isoflurane or sevoflurane anaesthesia, median nerve stimulation causes cortical responses of two kinds: an N20 wave with a latency of 20 ms and an EEG burst with a latency of 200 ms. We tested the possibility that median nerve stimulation during EEG suppression with propofol would cause an EEG response that was consistent enough to be of use for neuromonitoring. METHODS: Eight patients were anaesthetized with propofol to allow burst suppression. Electrical stimulation of the median nerve was applied during general anaesthesia and the EEG was measured. RESULTS: The EEG response to a painful stimulus had four successive components: (i) N20 and P22 potentials, reflecting activation of fast somatosensory pathways; (ii) a high-amplitude negative wave, possibly reflecting activation of the somatosensory cortex SII bilaterally; (iii) a burst (i.e. a negative slow wave with superimposed 10 Hz activity, probably reflecting an arousal mechanism); and (iv) a 13-15 Hz spindle, probably originating from the thalamus, similar to sleep spindles. These could be seen separately and in different combinations. Bursts and spindles during burst suppression were also seen without stimulation. In deepening propofol anaesthesia, spindles were seen in the continuous EEG before burst suppression was achieved. In deep anaesthesia, spindles were seen when bursts had ceased, and painful stimuli evoked sharp waves without subsequent bursts. CONCLUSION: In addition to SSEP (somatosensory evoked potentials), three different evoked responses are noted that could be useful for clinical monitoring.

Adult↗
PubMed2003

Spontaneous magnetism of quantum dot lattices.

The magnetism of square lattices of quantum dots with up to 12 electrons per dot is studied using the spin-density functional formalism. At small values of the lattice constant, all lattices are nonmagnetic and gapless. When the lattice constant is increased, the shell structure of the single dots governs the magnetism of the lattice. At closed shells, the lattices are nonmagnetic and have a gap at the Fermi level. At the beginning and at the end of a shell, they become ferromagnetic and stay gapless up to large values of the lattice constant. Antiferromagnetism was observed only at midshell after a band gap was opened.

Journal Article↗
PubMed2003

The role of various biomarkers in the evaluation of styrene genotoxicity.

We evaluated our data on the occupational exposure to styrene in lamination workers. The battery of parameters included markers of external and internal exposure and biomarkers of biological effects and susceptibility. DNA repair capacities have been determined in both exposed and control groups. Styrene workplace concentration significantly correlated with styrene concentration in blood, exhaled air and urinary mandelic acid. Haemoglobin and O(6)-styrene oxide (SO)-guanine DNA adducts were significantly higher in exposed subjects as compared to controls and correlated with exposure parameters. In styrene-exposed workers 1-SO-adenine DNA adducts were detected (2.6 per 10(9) dNp), while in controls these adducts were below the detection limit. 1-SO-adenine adduct levels were affected by both acute and cumulative exposure (P=0.001, F=86.0 and P=0.017, F=59.0, respectively) and associated with cytochrome P450 2E1 (CYP2E1) polymorphisms (R(2)=0.442). Mutant frequencies (MF) at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus appeared to accumulate with exposure over time and were associated with glutathione S-transferase P1 (GSTP1) polymorphism. DNA repair capacity increased with the exposure, except for the group exposed to the highest styrene concentration. In this particular group, increased DNA repair capacity to remove oxidative DNA damage was found.

Adult↗
PubMed2003

Effects of hypertonic saline (7.5%) on extracellular fluid volumes in healthy volunteers.

This study evaluated the effects of 7.5% saline on plasma and other extracellular fluid volumes. After baseline measurements, eight healthy postmenopausal female volunteers received 4 ml.kg-1 of hypertonic saline over 30 min. After the fluid infusion, the volunteers were studied for 60 min. Plasma volume was measured using a dilution of 125-iodine-labelled human albumin. Extracellular water and cardiac output were measured by whole body impedence cardiography. The infused volume was 4 ml.kg-1 (average 260 ml). Plasma volume increased rapidly during the infusion (mean +/- standard deviation, 442 +/- 167 ml). At the end of the 1-h follow-up period, plasma volume had increased by on average 465 ml (SD 83). The increase of extracellular water at the end of infusion and at the end of study was 650 ml (SD 93) and 637 ml (SD 192), respectively. The highest serum sodium recorded in the volunteers was 158 mmol.l-1. The effect of 7.5% saline on plasma volume was rapid and lasted for at least 1 h. Plasma volume remained elevated by more than the infused volume at the end of the study. The increase in plasma and extracellular fluid volumes was partly achieved by mobilizing intracellular water to extracellular compartment.

Aged↗
PubMed2001

Kinetics of formation of specific styrene oxide adducts in double-stranded DNA.

The possible carcinogenicity of styrene is believed to be related to the DNA-binding properties of styrene 7,8-oxide (SO). In order to compare the intrinsic reactivity of the different nucleophilic sites in DNA towards SO and to evaluate the candidates for human biomonitoring we have determined the second-order rate constants and stabilities of several SO-adducts in double-stranded DNA. These include alpha- and beta-isomers of N7-substituted and alphaN(2)-substituted guanines, alpha- and betaN3-substituted and alphaN(6)-substituted adenines as well as betaN3- and alphaN(4)-substituted cytosines. The highest rate constants were found for the spontaneously depurinating N7-guanines being ca. 3-15-fold higher than those for the stable adducts. When the relative proportions of different alkylation products were determined in course of time, after a single addition of SO, the labile N7-guanines and N3-adenines were the major products at early time points. After 144 h of incubation at 37 degrees C, alphaN(6)-SO-adenine and alphaN(2)-SO-guanine as well as betaN3-SO-uracil were the major adducts. Regarding human biomonitoring, the N7-substituted guanines should be one of the main targets because of the high reactivity of the N7-atom of guanine. However, in the case of chronic styrene exposures the chemically more stable DNA adducts may become important.

Alkylation↗
PubMed2001

Association between genetic polymorphisms and biomarkers in styrene-exposed workers.

A comprehensive approach to evaluate genotoxic effects induced by styrene exposure was employed in 44 hand-lamination workers in comparison with 18 unexposed controls. The acquired data on single-strand breaks in DNA (SSBs), frequency of chromosomal aberrations and HPRT mutant frequency in peripheral blood lymphocytes were compared to the results on genotyping of some of the xenobiotic-metabolising enzymes (CYP1A1, CYP2E1, epoxide hydrolase and GSTM1, GSTP1 and GSTT1). Multifactorial regression analysis indicated that SSB in DNA were significantly associated with styrene exposure and with heterozygosity in CYP2E1 (5'-flanking region and intron 6; r(2)=0.614). The frequency of chromosomal aberrations (CA), as analysed by linear multiple regression analysis, significantly correlated with years of employment (P=0.004) and with combinations of epoxide hydrolase (EPHX) genotypes (exon 3, Tyr/His and exon 4, His/Arg), where individuals with low and medium activity EPHX genotypes exhibited higher frequencies of CA than those with high activity genotypes (P=0.044, r(2)=0.563). Moderately higher HPRT mutant frequencies were detected in styrene-exposed individuals (20.2 +/- 25.8 x 10(-6)) as compared to controls (13.3 +/- 6.3 x 10(-6)), but this difference was not significant. ANOVA (in the whole set of data) revealed that mutant frequencies at the HPRT gene were significantly associated with years of employment (F=6.9, P=0.0001), styrene in blood (F=10.1, P=0.0001), and heterozygosity in CYP2E1 (intron 6; F=13.5, P=0.0008) and GSTP1 (exon 5; F=3.6, P=0.038). In conclusion, our present data suggest that analysed biomarkers of DNA damage may be modulated by polymorphic CYP2E1, EPHX and GSTP1. In our study, styrene-specific DNA and haemoglobin adducts are under investigation. Completing these data with the results of genotyping of metabolising enzymes may provide a useful tool for individual genotoxic risk assessment.

Adult↗
PubMed2001

DNA adducts, strand breaks and micronuclei in mice exposed to styrene by inhalation.

Genotoxic and clastogenic effects of styrene were studied in mice. Male NMRI mice were exposed by inhalation to styrene in concentrations of 750 and 1500 mg/m3 for 21, 7, 3 and 1 days (6 h/day, 7 days/week). Followed parameters included styrene in blood, specific styrene oxide (SO) induced DNA adducts, DNA strand breaks and micronuclei. The formation of SO induced 7-SO-guanines and 1-SO-adenines in DNA was analysed from lung tissues by two versions of the 32P-postlabeling technique. In lungs after 21 days of exposure to 1500 mg/m3 the level of 7-SO-guanine was 23.0+/-11.9 adducts/10(8) normal nucleotides, while 1-SO-adenine was detected at the levels of 0.6+/-0.2 adducts/10(8) normal nucleotides. Both 7-SO-guanines and 1-SO-adenines strongly correlated with exposure parameters, particularly with styrene concentration in blood (r=0.875, P=0.0002 and r=0.793, P=0.002, respectively). DNA breaks were measured in peripheral lymphocytes, bone marrow cells and liver cells using comet assay. To discern oxidative damage and abasic sites, endonuclease III was used. In bone marrow of exposed mice slight increase of strand breaks can be detected after 7 days of inhalation. A significant increase was revealed in the endonuclease III-sensitive sites after 21 days of inhalation in bone marrow. In the liver cells inhalation exposure to both concentrations of styrene did not virtually affect either levels of DNA single-strand breaks or endonuclease III-sensitive sites. The inhalation of 1500 mg/m3 of styrene induced significant increase of micronuclei after 7 days of exposure (10.4+/-2.5/1000 cells, i.e. twice higher micronuclei frequency than in controls). After 21 days of inhalation no significant difference between the control group and the two exposed groups was observed. Whether the decrease of micronuclei after 21 days of inhalation was due to the inhibition of cell proliferation caused by styrene or due to the natural elimination of chromatide fragments, remains to be clarified. An interesting link has been found between DNA single-strand breaks in bone marrow and frequencies of micronuclei (r=0.721, P=0.028).

Administration, Inhalation↗
PubMed2001

Propofol anesthesia induces phase synchronization changes in EEG.

OBJECTIVE: Phase coupling between EEG channel pairs in various frequency bands was evaluated during propofol anesthetic induction and recovery periods. METHODS: Twenty-three patients participated in the study. Phase synchronization indices based on the Hilbert transform were investigated on frequency bands 0.05-1 Hz, 1-4 Hz, 4-8 Hz, 8-12 Hz and 12-16 Hz for all pairs of the 9 EEG channels covering midline and frontal areas. A straight line was used to approximate the index values as a function of time and the Sign Test statistics were applied to the slope parameters. RESULTS: Systematic phase synchronization changes were detected. Generally, phase synchronization in the sub-delta band decreased during the induction and increased during the recovery, while the directions were reversed in the alpha band. The changes were dependent on the channel pair. In the delta, theta and beta bands, the changes were aligned more irregularly than in the sub-delta or in the alpha bands. Highly asymmetric behavior between the induction and the recovery periods was also observed in these bands. CONCLUSIONS: Induction and recovery from propofol anesthesia changes the phase synchronization between the EEG channels. The passband and location-specific behavior of these changes reveals the effects of the anesthetic to the different neural mechanisms.

Adult↗
PubMed2001

Effects of hypertonic saline (7.5%) on extracellular fluid volumes compared with normal saline (0.9%) and 6% hydroxyethyl starch after aortocoronary bypass graft surgery.

OBJECTIVE: To compare the effects of hypertonic (7.5%) saline (HS), normal (0.9%) saline (NS), and 6% hydroxyethyl starch (HES) on extracellular fluid volumes in the early postoperative period after cardiopulmonary bypass. DESIGN: A prospective, randomized, double-blind study. SETTING: University teaching hospital. PARTICIPANTS: Forty-eight patients scheduled for elective coronary artery bypass graft surgery. INTERVENTIONS: Patients were randomly allocated to receive 4 mL/kg of HS, NS, or HES during 30 minutes when volume loading was needed during the postoperative rewarming period in the intensive care unit. Plasma volume was measured using a dilution of iodine-125-labeled human serum albumin. Extracellular water and cardiac output were measured by whole-body impedance cardiography. MEASUREMENTS AND MAIN RESULTS: Plasma volume had increased by 19 +/- 7% in the HS group and by 10 +/- 3% in the NS group (p = 0.001) at the end of the study fluid infusion. After 1-hour follow-up time, the plasma volume increase was greatest (23 +/- 8%) in the group receiving HES (p < 0.001). The increase of extracellular water was greater than the infused volume in the HS and HES groups at the end of the infusion. One-hour diuresis after the study infusion was greater in the HS group (536 +/- 280 mL) than in the NS (267 +/- 154 mL, p = 0.006) and HES groups (311 +/- 238 mL, p = 0.025). CONCLUSION: The effect of HS on plasma volume was short-lasting, but it stimulated excretion of excess body fluid accumulated during cardiopulmonary bypass and cardiac surgery. HS may be used in situations in which excess free water administration is to be avoided but the intravascular volume needs correction.

Aged↗
PubMed2001

Dysphagia and oesophageal clearance after laparoscopic versus open Nissen fundoplication. A randomized, prospective trial.

BACKGROUND: An increase in postoperative dysphagia has been reported after laparoscopic fundoplication. Our aim was to compare laparoscopic Nissen-Rossetti fundoplication to open fundoplication regarding oesophageal clearance and dysphagia in a prospective, randomized study. METHODS: Twenty-eight consecutive patients with objectively observed gastro-oesophageal reflux disease referred to operative treatment were randomized to laparoscopic (13) or open (15) fundoplication. A standard formula was used in pre- and postoperative interview. Oesophageal clearance was measured by liquid bolus radionuclide transit before and 3 days, 1 month and 1 year after fundoplication. Endoscopy was done preoperatively and 1 year after the operation. RESULTS: Heartburn, regurgitation and ooesophagitis were cured with equal effectiveness (p = 0.001). New-onset dysphagia was observed in nine (69%) of the patients in the laparoscopic group and in nine (60%) in the open group during the first postoperative month. Food impaction occurred in four (31%) cases after laparoscopic and in two (13%) after open surgery (ns). One year after the operation, one patient (8%) in both groups had more than mild symptoms. Oesophageal radionuclide transit remained normal after open fundoplication, but after the laparoscopic procedure oesophageal clearance was disturbed--only one patient did not have a pathologic result during the first postoperative month. One year after the operation, clearance was normal. CONCLUSIONS: After laparoscopic operation, a tendency to more severe new-onset dysphagia was observed, and oesophageal clearance was transiently disturbed. Efforts should be made to minimize postoperative swallowing and clearance disturbances after laparoscopic fundoplication in order to get the full value out of otherwise more rapid recovery.

Deglutition Disorders↗
PubMed2001

Psychometric properties of the Finnish 20-item Toronto Alexithymia Scale.

The aim of this study was to examine the factor structure and the validity of the Finnish version of the 20-item Toronto Alexithymia Scale (TAS-20). As part of the Northern Finland 1966 Birth Cohort Project, the TAS-20 was presented to a sample of 5034 31-year old persons. A confirmatory factor analysis showed that the three-factor model, earlier established with the original TAS-20, was in agreement with the Finnish version of the scale. Three criteria of goodness-of-fit met the standards for adequacy of fit. For the total scale, internal reliability (Cronbach's alpha) was 0.83 and for the three subscales (factors 1, 2, and 3) it was 0.81, 0.77, and 0.66, respectively. Two- and one-factor models for TAS-20 were also examined, but the other models did not perform as well as the three-factor model. The factor model also worked well with a sample of 516 students with a mean age of 24.8 years. In conclusion, the TAS-20 scale is useful in the Finnish version, too.

Adult↗
PubMed2001

Identification of 1-adenine DNA adducts in workers occupationally exposed to styrene.

Styrene is an extensively used industrial chemical that has been classified as a possible human carcinogen. The possible carcinogenicity may be related to the covalent DNA binding properties of styrene 7,8-oxide, a major metabolite of styrene. We have developed a sensitive and a highly specific phosphorus-32-postlabeling method for the determination of 1-styrene 7,8-oxide-adenine DNA adducts. These adducts were analyzed in white blood cells from workers exposed to styrene at mean level of 76.2 mg/m3. Three of nine exposed workers showed adducts above the detection limit; the mean was 0.79 +/- 0.14 1-styrene 7,8-oxide-adenine DNA adducts/10(9) nucleotides. None of the 11 control cells showed adducts above the detection limit, which was 0.4 adducts/10(9) nucleotides. The results show a potential of 1-adenine DNA adducts for predicting risks in the workers exposed to styrene.

Adenine↗