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Biomedical subjects

A Virtanen

Publications and source records attributed to A Virtanen.

At least 19 recordsLinked to original sources
PubMed2006

Aminoglycoside interactions with RNAs and nucleases.

One of the major challenges in medicine today is the development of new antibiotics as well as effective antiviral agents. The well-known aminoglycosides interact and interfere with the function of several noncoding RNAs, among which ribosomal RNAs (rRNAs) are the best studied. Aminoglycosides are also known to interact with proteins such as ribonucleases. Here we review our current understanding of the interaction between aminoglycosides and RNA. Moreover, we discuss briefly mechanisms behind the inactivation of aminoglycosides, a major concern due to the increasing appearance of multiresistant bacterial strains. Taken together, the general knowledge about aminoglycoside and RNA interaction is of utmost importance in the process of identifying/developing the next generation or new classes of antibiotics. In this perspective, previously unrecognized as well as known noncoding RNAs, apart from rRNA, are promising targets to explore.

Aminoglycosides↗
PubMed2005

Improved fibrinolysis by an intensive lifestyle intervention in subjects with impaired glucose tolerance. The Finnish Diabetes Prevention Study.

AIMS/HYPOTHESIS: The aim of this study was to investigate the effects of lifestyle intervention on the levels of plasminogen activator inhibitor (PAI-1) and fibrinogen in subjects participating in the Finnish Diabetes Prevention Study (DPS). METHODS: In five DPS centres, 321 subjects with impaired glucose tolerance (intervention group, n=163; control group, n=158) had their PAI-1 and fibrinogen levels measured at baseline and at the 1-year follow-up. Additional 3-year follow-up assessments were carried out in a sample of 97 subjects in one of the DPS centres (Turku). The intervention programme included an intensive lifestyle intervention aiming at weight reduction, healthy diet and increased physical activity. RESULTS: During the first intervention year, PAI-1 decreased by 31% in the intervention group but showed no change in the control group (p<0.0001). In the Turku subgroup, the decrease in PAI-1 persisted throughout the 3-year follow-up. Changes in PAI-1 were associated with the number of lifestyle changes made during the first year (p=0.008). Weight reduction was the most important factor explaining the decrease in PAI-1. Changes in fibrinogen levels did not differ between the groups. CONCLUSIONS/INTERPRETATION: In addition to the previously reported reduction in the risk of type 2 diabetes in DPS participants with impaired glucose tolerance, the intensive dietary and exercise intervention had beneficial long-term effects on fibrinolysis as indicated by the reduced levels of PAI-1. These results suggest that elevated PAI-1 levels in obese subjects with impaired glucose tolerance are mostly reversible by lifestyle changes, especially those geared to weight reduction.

Adult↗
PubMed2005

Adoption of celecoxib and rofecoxib: a nationwide database study.

BACKGROUND AND OBJECTIVE: Cyclooxygenase 2-selective non-steroidal anti-inflammatory drugs (NSAIDs, coxibs) are recommended primarily for patients at high risk of gastrointestinal bleeding, most of them being elderly. Our objective was to describe and analyse patient- and physician-related factors affecting the adoption of celecoxib and rofecoxib 2 years after their launch in Finland. METHODS: Retrospective analysis of the nationwide Prescription Register. Physicians who had issued at least 200 reimbursed prescriptions in 2002 (n = 12 033, 80% of working-age Finnish physicians) were involved in the analysis. RESULTS AND DISCUSSION: Excluding patients with rheumatoid arthritis (RA), almost one-fifth (18%) of NSAIDs prescriptions were for coxibs. In patients with RA the share was 25%. The share of coxib prescriptions of all NSAIDs increased with age of the patient. Over one half (58%) of coxib prescriptions were issued for patients under 65 years of age. Specialists in physical and rehabilitation medicine were the fastest adopters of coxibs: one-third of their NSAID prescriptions in 2002 were for coxibs. Primary care physicians were the most conservative both in adopting and favouring coxibs. CONCLUSIONS: Coxibs have gained the status of standard prescription NSAIDs within a few years. Their use should be restricted to patients who could benefit most from the use. Routine prescribing of expensive new drugs increases the drug bill without additional health gain.

Age Factors↗
PubMed2004

Effects of a 6-month exercise program on patients with multiple sclerosis: a randomized study.

OBJECTIVE: To improve walking and other aspects of physical function with a progressive 6-month exercise program in patients with multiple sclerosis (MS). METHODS: MS patients with mild to moderate disability (Expanded Disability Status Scale scores 1.0 to 5.5) were randomly assigned to an exercise or control group. The intervention consisted of strength and aerobic training initiated during 3-week inpatient rehabilitation and continued for 23 weeks at home. The groups were evaluated at baseline and at 6 months. The primary outcome was walking speed, measured by 7.62 m and 500 m walk tests. Secondary outcomes included lower extremity strength, upper extremity endurance and dexterity, peak oxygen uptake, and static balance. An intention-to-treat analysis was used. RESULTS: Ninety-one (96%) of the 95 patients entering the study completed it. Change between groups was significant in the 7.62 m (p = 0.04) and 500 m walk tests (p = 0.01). In the 7.62 m walk test, 22% of the exercising patients showed clinically meaningful improvements. The exercise group also showed increased upper extremity endurance as compared to controls. No other noteworthy exercise-induced changes were observed. Exercise adherence varied considerably among the exercisers. CONCLUSIONS: Walking speed improved in this randomized study. The results confirm that exercise is safe for multiple sclerosis patients and should be recommended for those with mild to moderate disability.

Adult↗
PubMed2004

Sensory regeneration following intraoperatively verified trigeminal nerve injury.

OBJECTIVE: To follow recovery of sensory function mediated by both myelinated and unmyelinated axons in relation to the type of inferior alveolar nerve (IAN) injury. METHODS: The authors assessed the function of afferent Abeta-, Adelta-, and C-fibers of the IAN using neurophysiologic (mental nerve blink reflex, sensory nerve conduction [NCS] of the IAN) and quantitative sensory tests (QST; cold, warm, heat pain, and tactile modalities). The tests were done 2 weeks, 1, 3, 6, and 12 months postoperatively and compared to the preoperative baseline in 20 patients undergoing mandibular bilateral sagittal split osteotomy. Nineteen patients underwent intraoperative monitoring. RESULTS: In primarily demyelinating injuries (21/40 nerves), the sensory alteration and all tests normalized on the group level within the first 3 months. After partial axonal lesions (15/40 nerves), neurophysiologic and thermal QST results remained abnormal at 1-year control in a high proportion of the IAN distributions (up to 67%). At 1 year, the tactile QST was abnormal in 40%, but the NCS in 87% of the symptomatic IAN distributions. Neuropathic pain occurred in 5% of the patients, only after severe axonal damage. CONCLUSIONS: Sensory nerve conduction and thermal quantitative sensory testing showed incomplete sensory regeneration at 1 year after axonal trigeminal nerve damage. Clinical examination with tactile quantitative sensory testing was less reliable in the follow-up of sensory recovery. Sensory Abeta-, Adelta-, and C-fibers recovered function at similar rates. The trigeminal nerve does not differ from other peripheral nerves as regards susceptibility to neuropathic pain.

Action Potentials↗
PubMed2004

Exercise capacity, disability and leisure physical activity of subjects with multiple sclerosis.

The purpose of the present study was to examine exercise capacity and its relationship to neurological disability as measured using the Expanded Disability Status Scale (EDSS) and to leisure physical activity in subjects with multiple sclerosis (MS). Thirty-four men and 61 women (mean age 44 +/- 6.7 years, mean disease duration 5.7 +/- 6.4 years) with mild to moderate disability (EDSS range 1.0-5.5) participated. They underwent an incremental exercise test on a leg cycling ergometer. Leisure physical activity was measured using a questionnaire. Peak oxygen uptake (VO2peak) in men was 27.0 +/- 5.2 mL/kg/min, and in women 21.7 +/- 5.5 mL/kg/min. The disability correlated inversely with the VO2peak both in men (r = - 0.50, P = 0.004) and in women (r = - 0.25, P = 0.05). No correlation between disease duration and VO2peak was found. In a multivariate regression analysis, neurological disability was confirmed as a predictor of VO2peak. No evidence of a relationship between leisure physical activity and VO2peak was found. A main finding was that disability and exercise capacity are inter-related, even in subjects who are not severely handicapped (84% had an EDSS of < 4.0). The level of disability should be taken into account in the planning of aerobic exercise programs for fully ambulatory MS subjects.

Adult↗
PubMed2003

Maternal midtrimester free beta-HCG and AFP serum levels in spontaneous singleton pregnancies complicated by gestational diabetes mellitus, pregnancy-induced hypertension or obstetric cholestasis.

OBJECTIVES: The present study aims at finding out whether a connection exists between altered serum free beta-hCG and/or alpha-fetoprotein (AFP) levels and the manifestation of specific pregnancy complications [i.e. gestational diabetes mellitus (GDM), pregnancy induced hypertension (PIH) or intrahepatic cholestasis of pregnancy (ICP)]. METHODS: We compared free beta-hCG and AFP multiples of median (MoM) values in singleton pregnancies. The study population consisted of 117 pregnancies with GDM, 107 with PIH and 24 with ICP. The control group consisted of 1148 singleton pregnancies without any pregnancy complications. All were spontaneously conceived. RESULTS: In the group with GDM, both the free beta-hCG (0.72 MoM) and AFP MoM values (0.93) were significantly lower than in controls (beta-hCG 0.97 MoM, p = 0.0063 and AFP 1.01 MoM, p = 0.01). No statistically significant differences in the marker levels were observed between the ICP pregnancies and the control group. CONCLUSIONS: GDM has an impact on maternal midtrimester free beta-hCG and AFP levels and may change the DS screening result.

Adult↗
PubMed2003

An evaluation of clinical and electrophysiologic tests in nerve injury diagnosis after mandibular sagittal split osteotomy.

The yield of clinical sensory tests and electrophysiologic tests in the diagnostics of inferior alveolar nerve (IAN) damage after bilateral sagittal split osteotomy (BSSO) was studied. The diagnostic value of these tests was evaluated by comparing the test results to the degree of nerve damage at the end of the operation as documented by means of the intraoperative nerve conduction recording of the IAN. Twenty patients undergoing BSSO were analysed preoperatively and 2 weeks postoperatively. The frequency of the IAN disturbance ranged from 10% to 94% depending on the test method and the test site used. Of the clinical sensory tests, the touch detection threshold (TD) test was the most sensitive and clinically useful test. It also correlated best with the electrophysiologically verified intraoperative nerve damage (R = -0.603, P = 0.017 on the right, R = -0.626, P = 0.01 on the left). The blink reflex and quantitative cold detection threshold tests were almost as often abnormal as the TD-test, but nerve conduction study (NCS) was the most sensitive (88%) of all clinical and electrophysiologic tests. The frequency of abnormal findings in the electrophysiologic tests indicating IAN injury, 75% on the right side and 90% on the left side, corresponded exactly with the figures of subjective sensory alteration. Almost all electrophysiologic tests showed obvious associations with the objectively verified IAN damage. All tests, except the NCS, showed only moderate sensitivity. Specificity of the tests was generally high, the only exceptions being the TD test and the NCS. To increase the diagnostic accuracy of the testing and to detect different types of damage in different nerve fibre populations, a combination of different sensory and electrophysiologic tests is recommended.

Action Potentials↗
PubMed2002

Risk factors of nerve injury during mandibular sagittal split osteotomy.

There is little objective data about whether surgical technique or mandibular anatomy are a risk for inferior alveolar nerve (IAN) injury during bilateral sagittal split osteotomy (BSSO). Orthodromic sensory nerve action potentials (SNAPs) of the IAN were continuously recorded on both sides in 20 patients with mandibular retrognathia during BSSO operation. Changes in latency, amplitude, and sensory nerve conduction velocity (SNCV) at baseline and at different stages of the operation were analyzed. The SNAP latencies prolonged, the amplitudes diminished, and the SNCVs slowed down during BSSO (P = 0.0000 for all parameters). The most obvious changes occurred during surgical procedures on the medial side of the mandibular ramus. There was a clear tendency towards more disturbed IAN conduction with longer duration of these procedures (right side R = -0.529. P = 0.02; left side R = -0.605, P = 0.006). Exposure or manipulation of the IAN usually had no effect on nerve function, but the IAN conduction tended to be more disturbed in cases with nerve laceration. Low corpus height (R = 0.802, P = 0.001) and the location of the mandibular canal near the inferior border of the mandible (R = 0.52, P = 0.02) may increase the risk of IAN injury. There was no correlation between the age of the patients and the electrophysiological grade of nerve damage.

Action Potentials↗
PubMed2002

Serum free beta-HCG and alpha-fetoprotein levels in IVF, ICSI and frozen embryo transfer pregnancies in maternal mid-trimester serum screening for Down's syndrome.

BACKGROUND: The aim of this study was to compare the maternal mid-trimester free beta-HCG and alpha-fetoprotein (AFP) levels in pregnancies conceived by assisted reproduction technology and spontaneous pregnancies in Down's syndrome screening. The influence of the number of embryos transferred and the amount of gonadotrophins used on the marker levels was also evaluated. METHODS: The study population consisted of 58 IVF, 32 ICSI and 26 frozen embryo transfer (FET) singleton pregnancies. The levels of beta-HCG and AFP were compared with the control group of 6548 singleton spontaneous pregnancies. RESULTS: The false positive rate (FPR) in the Down's syndrome screening was 19% overall in assisted reproductive technology pregnancies, being highest (30.8%) in the FET group. The free beta-HCG multiples of the median (MoM) values were statistically significantly elevated only in the FET group (1.33 MoM; P = 0.012). A positive correlation between the number of embryos transferred and the marker levels was observed in the IVF group. No correlation was found between the amount of gonadotrophin medication used and the marker levels. CONCLUSIONS: The present data confirm that the overall FPR in the serum screening for Down's syndrome in assisted reproduction pregnancies is high, resulting in unnecessary invasive procedures.

Adult↗
PubMed2001

A novel nuclear human poly(A) polymerase (PAP), PAP gamma.

Poly(A) polymerase (PAP) is present in multiple forms in mammalian cells and tissues. Here we show that the 90-kDa isoform is the product of the gene PAPOLG, which is distinct from the previously identified genes for poly(A) polymerases. The 90-kDa isoform is referred to as human PAP gamma (hsPAP gamma). hsPAP gamma shares 60% identity to human PAPII (hsPAPII) at the amino acid level. hsPAP gamma exhibits fundamental properties of a bona fide poly(A) polymerase, specificity for ATP, and cleavage and polyadenylation specificity factor/hexanucleotide-dependent polyadenylation activity. The catalytic parameters indicate similar catalytic efficiency to that of hsPAPII. Mutational analysis and sequence comparison revealed that hsPAP gamma and hsPAPII have similar organization of structural and functional domains. hsPAP gamma contains a U1A protein-interacting region in its C terminus, and PAP gamma activity can be inhibited, as hsPAPII, by the U1A protein. hsPAPgamma is restricted to the nucleus as revealed by in situ staining and by transfection experiments. Based on this and previous studies, it is obvious that multiple isoforms of PAP are generated by three distinct mechanisms: gene duplication, alternative RNA processing, and post-translational modification. The exclusive nuclear localization of hsPAP gamma establishes that multiple forms of PAP are unevenly distributed in the cell, implying specialized roles for the various isoforms.

Alternative Splicing↗
PubMed2001

The mRNA cap structure stimulates rate of poly(A) removal and amplifies processivity of degradation.

Poly(A)-specific ribonuclease (PARN) is an oligomeric, processive, and cap-interacting 3' exonuclease. We have studied how the m7G(5')ppp(5')G cap structure affects the activity of PARN. It is shown that the cap has four distinct effects: (i) It stimulates the rate of deadenylation if provided in cis; (ii) it inhibits deadenylation if provided at high concentration in trans; (iii) it stimulates deadenylation if provided at low concentration in trans; and (iv) it increases the processivity of PARN when provided in cis. It is shown that the catalytic and cap binding sites on PARN are separate. The important roles of the 7-methyl group and the inverted guanosine residue of the cap are demonstrated. An active deadenylation complex, consisting of the poly(A)-tailed RNA substrate and PARN, has been identified. Complex formation does not require a cap structure on the RNA substrate. The multiple effects of cap are all accounted for by a simple, kinetic model that takes the processivity of PARN into account.

Chromatography, Thin Layer↗
PubMed2001

Aminoglycoside binding displaces a divalent metal ion in a tRNA-neomycin B complex.

Aminoglycosides bind to RNA and interfere with its function, and it has been suggested that aminoglycoside binding to RNA displaces essential divalent metal ions. Here we demonstrate that addition of various aminoglycosides inhibited Pb2+-induced cleavage of yeast tRNA(Phe). Cocrystallization of yeast tRNA(Phe) and an aminoglycoside, neomycin B, resulted in crystals that diffracted to 2.6 A and the structure of the complex was solved by molecular replacement. The structure shows that the neomycin B binding site overlaps with known divalent metal ion binding sites in yeast tRNA(Phe), providing direct evidence for the hypothesis that aminoglycosides displace metal ions. Additionally, the neomycin B binding site overlaps with major determinants for Escherichia coli phenylalanyl-tRNA-synthetase. Here we present data demonstrating that addition of neomycin B inhibited aminoacylation of E. coli tRNA(Phe) in the mid microM range. Given that aminoglycoside and metal ion binding sites overlap, we discuss that aminoglycosides can be considered as 'metal mimics'.

Acylation↗
PubMed2000

A 54-kDa fragment of the Poly(A)-specific ribonuclease is an oligomeric, processive, and cap-interacting Poly(A)-specific 3' exonuclease.

We have previously identified a HeLa cell 3' exonuclease specific for degrading poly(A) tails of mRNAs. Here we report on the purification and identification of a calf thymus 54-kDa polypeptide associated with a similar 3' exonuclease activity. The 54-kDa polypeptide was shown to be a fragment of the poly(A)-specific ribonuclease 74-kDa polypeptide. The native molecular mass of the nuclease activity was estimated to be 180-220 kDa. Protein/protein cross-linking revealed an oligomeric structure, most likely consisting of three subunits. The purified nuclease activity released 5'-AMP as the reaction product and degraded poly(A) in a highly processive fashion. The activity required monovalent cations and was dependent on divalent metal ions. The RNA substrate requirement was investigated, and it was found that the nuclease was highly poly(A)-specific and that only 3' end-located poly(A) was degraded by the activity. RNA substrates capped with m(7)G(5')ppp(5')G were more efficiently degraded than noncapped RNA substrates. Addition of free m(7)G(5')ppp(5')G cap analogue inhibited poly(A) degradation in vitro, suggesting a functional link between the RNA 5' end cap structure and poly(A) degradation at the 3' end of the RNA.

Adenosine Monophosphate↗
PubMed2000

Alterations in laboratory test results during adjuvant breast cancer treatment.

An increasing number of women is treated with adjuvant cyclophosphamide, methotrexate and 5-fluorouracil therapy for breast cancer. The effects of the chemotherapy on many laboratory tests are, however, inadequately known. This study investigates the effects of the treatment on various laboratory tests. Fifteen premenopausal women receiving adjuvant cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy and optional radiotherapy were included in the study. Common hormonal, biochemical, hematological, protein and lipid laboratory tests were taken serially during a 10-month follow-up. Twelve women became amenorrheic. Their serum follicle stimulating hormone and luteinising hormone concentrations increased accordingly. Other serum hormones (testosterone, androstenedione, sex hormone-binding globulin, prolactin, dehydroepiandrosterone sulfate, cortisol, parathyroid hormone and thyroid hormones) changed only slightly. Hemoglobin concentration and white blood cell count decreased slightly. Serum alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase, angiotensin-converting enzyme, amylase, glucose, potassium, phosphate, urea and triglycerides concentrations increased slightly whereas serum bilirubin, haptoglobin, and immunoglobulin A and M decreased slightly. Serum alpha1-antitrypsin fluctuated around the baseline concentration. Other test results remained at their pretreatment concentrations. With the exception of increases in serum gonadotrophins, the changes observed were slight and the mean concentrations remained within reference limits. Therefore, cyclophosphamide, methotrexate and 5-fluorouracil adjuvant treatment is unlikely to complicate the diagnosis of other diseases.

Adult↗