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Biomedical subjects

J Mikkola

Publications and source records attributed to J Mikkola.

At least 19 recordsLinked to original sources
PubMed2003

Reactive arthritis after an outbreak of Yersinia pseudotuberculosis serotype O:3 infection.

OBJECTIVE: To determine the occurrence and clinical characteristics of reactive arthritis (ReA) after an outbreak of Yersinia pseudotuberculosis serotype O:3 infection. METHODS: From 15 October to 6 November 1998, a widespread outbreak of Y pseudotuberculosis serotype O:3 occurred in Finland. A questionnaire on musculoskeletal symptoms was mailed to 38 patients with infection confirmed by culture. All patients who reported joint symptoms were interviewed by phone and their medical records of outpatient visits or hospital admission because of recent joint symptoms were reviewed. RESULTS: Thirty three of 38 (87%) patients returned the questionnaire. Reactive musculoskeletal symptoms were reported by 5/33 (15%): four patients (12%) fulfilled the criteria for ReA and one additional patient had reactive enthesopathy. The patients with ReA were adults (age range 40-47 years), whereas the patient with reactive enthesopathy was a 14 year old boy. In all patients with ReA, the arthritis was polyarticular. In addition to peripheral arthritis, other musculoskeletal symptoms included sacroiliitis (one patient), pain in Achilles tendon (one patient), and heel pain (two patients). HLA-B27 was positive in all the three patients tested. In three of four patients with ReA, the duration of acute arthritis was over six months. CONCLUSION: Y pseudotuberculosis serotype O:3 infection is frequently associated with ReA and the clinical picture is severe.

Adolescent↗
PubMed2002

Neuromuscular adaptations during concurrent strength and endurance training versus strength training.

The purpose of this study was to investigate effects of concurrent strength and endurance training (SE) (2 plus 2 days a week) versus strength training only (S) (2 days a week) in men [SE: n=11; 38 (5) years, S: n=16; 37 (5) years] over a training period of 21 weeks. The resistance training program addressed both maximal and explosive strength components. EMG, maximal isometric force, 1 RM strength, and rate of force development (RFD) of the leg extensors, muscle cross-sectional area (CSA) of the quadriceps femoris (QF) throughout the lengths of 4/15-12/15 (L(f)) of the femur, muscle fibre proportion and areas of types I, IIa, and IIb of the vastus lateralis (VL), and maximal oxygen uptake (VO(2max)) were evaluated. No changes occurred in strength during the 1-week control period, while after the 21-week training period increases of 21% (p<0.001) and 22% (p<0.001), and of 22% (p<0.001) and 21% (p<0.001) took place in the 1RM load and maximal isometric force in S and SE, respectively. Increases of 26% (p<0.05) and 29% (p<0.001) occurred in the maximum iEMG of the VL in S and SE, respectively. The CSA of the QF increased throughout the length of the QF (from 4/15 to 12/15 L(f)) both in S (p<0.05-0.001) and SE (p<0.01-0.001). The mean fibre areas of types I, IIa and IIb increased after the training both in S (p<0.05 and 0.01) and SE (p<0.05 and p<0.01). S showed an increase in RFD (p<0.01), while no change occurred in SE. The average iEMG of the VL during the first 500 ms of the rapid isometric action increased (p<0.05-0.001) only in S. VO(2max) increased by 18.5% (p<0.001) in SE. The present data do not support the concept of the universal nature of the interference effect in strength development and muscle hypertrophy when strength training is performed concurrently with endurance training, and the training volume is diluted by a longer period of time with a low frequency of training. However, the present results suggest that even the low-frequency concurrent strength and endurance training leads to interference in explosive strength development mediated in part by the limitations of rapid voluntary neural activation of the trained muscles.

Adaptation, Physiological↗
PubMed2002

Development of level A, B and C in vitro-in vivo correlations for modified-release levosimendan capsules.

The aim of this study was to investigate the possibility of developing different levels of correlation between in vitro release and in vivo absorption rate for four modified-release levosimendan capsule formulations. Differences and similarities in the in vitro dissolution curves were compared with pharmacokinetic parameters describing absorption rate. Formulations F, G, H and I differed in the amounts of the delaying excipients alginic acid and HPMC. In vitro release rate was studied by the USP basket method using the following conditions: pH 5.8 or 7.4 and a rotation speed of 50 or 100 rpm. In vivo bioavailability was tested in nine healthy male volunteers and the fractions absorbed were calculated by the Wagner-Nelson method. Dissolution conditions pH 5.8 and a rotation speed of 100 rpm predicted best the similarities and differences in absorption rates among different formulations, and levels C and B correlation coefficients were 0.85 and 0.97, respectively. For formulation H level A correlation (r=0.997) was found when in vitro lag time was 0.2 h and time scale factor 1.9. This study indicated that dissolution tests developed can be used as a surrogate for human bioequivalence studies, for development processes of final commercial products, to ensure batch to batch bioequivalence and in the future in possible scale-up and post approval change cases for modified-release levosimendan formulation H.

Adult↗
PubMed2001

Oxidized LDL and thickness of carotid intima-media are associated with coronary atherosclerosis in middle-aged men: lower levels of oxidized LDL with statin therapy.

We investigated the relation between serum lipids including oxidized LDL and the severity of coronary atherosclerosis. Serum lipids and oxidized LDL was measured in 62 men (33-66 years), who underwent diagnostic coronary angiography and sonography to measure the carotid intima-media thickness. LDL oxidation was found in chemical analyses to be due to conjugated fatty acids in cholesteryl esters and triglycerides. Regression analysis indicated that the carotid intima-media thickness and the ratio of LDL diene conjugation to LDL cholesterol (the ox-LDL:LDL ratio) were the only factors associated independently with the severity of coronary atherosclerosis. The patients with multi-vessel disease who did not use lipid lowering therapy had a 50% thicker carotid intima media (P = 0.030) and a 41% higher ox-LDL:LDL ratio (P = 0.020) than patients with normal vessels. Further, patients with multi-vessel disease on statin therapy had a 24% lower ox-LDL:LDL ratio than the subjects with multi-vessel disease who did not use lipid lowering drugs (P = 0.027), although the concentration of LDL cholesterol did not differ between the groups. This study supports the hypothesis that lipid oxidation plays a role in the development of atherosclerosis.

Adult↗
PubMed2001

Transthoracic color Doppler echocardiography: a new way to diagnose coronary artery disease.

Until now, transthoracic echocardiography (TTE) has had the capability to visualize only the proximal portions of the main coronary arteries. However, we noticed that transthoracic color Doppler echocardiography has marked potential to visualize flow in the coronary arteries. In clinical cases we tested whether this method is useful for visualizing stenoses and flow even in peripheral branches of the coronaries. This article presents two illustrative clinical cases. In our experience, transthoracic color Doppler echocardiography is very suitable for clinical use.

Adult↗
PubMed2001

Neurobiological processes in alcohol addiction.

This article represents the proceedings of a symposium at the ISBRA Meeting in Yokohama, Japan. The chairs were A. D. Lê and K. Kiianmaa. The presentations were (1) Alcohol reward and aversion, by C. L. Cunningham; (2) The role of sensitization of neuronal mechanisms in ethanol self-administration, by J. A. Engel, M. Ericson, and B. Söderpalm; (3) Alcohol self-administration in dependent animals: Neurobiological mechanisms, by G. F. Koob, A. J. Roberts, and F. Weiss; (4) Stress and relapse to alcohol, by A. D. Lê; (5) Alcohol-preferring AA and alcohol-avoiding ANA rats differ in locomotor activation induced by repeated morphine injections, by P. Hyytiä, S. Janhunen, J. Mikkola, P. Bäckström, and K. Kiianmaa; and (6) Initial sensitivity and acute functional tolerance to the hypnotic effects of ethanol in mice genetically selected for mild and severe ethanol withdrawal convulsions, by I. Ponomarev and J. C. Crabbe.

Alcoholism↗
PubMed2001

Glucuronidation of 1-hydroxypyrene by human liver microsomes and human UDP-glucuronosyltransferases UGT1A6, UGT1A7, and UGT1A9: development of a high-sensitivity glucuronidation assay for human tissue.

Human UDP-glucuronosyltransferases (UGT, EC 2.4.1.17) involved in the biotransformation of pyrene were investigated by a sensitive fluorometric high-performance liquid chromatography (HPLC)method developed for determining activities toward 1-hydroxypyrene. The endpoint metabolite of pyrene, 1-pyrenylglucuronide, is a well-known urinary biomarker for the assessment of human exposure to polycyclic aromatic hydrocarbons. 1-Pyrenylglucuronide was synthesized using rat liver microsomes as biocatalyst. The yield was satisfactory, 22%. 1-Pyrenylglucuronide, identified by (1)H NMR and by electrospray mass spectrometry, was used for method validation and calibration. The HPLC assay was very sensitive with a quantitation limit of 3 pg (8 fmol) for 1-pyrenylglucuronide. The assay was precise, showing a relative standard deviation of 5% or less at 0.1 to 300 microM 1-hydroxypyrene. Only 2 microg of microsomal protein was required for the assay in human liver. The glucuronidation of 1-hydroxypyrene was catalyzed at high rates in microsomes from pooled or three individual liver samples, showing comparable apparent K(m) values. The formation of 1-pyrenylglucuronide was catalyzed by recombinant human UGT1A6, UGT1A7, and UGT1A9, the K(m) values being 45, 12, and 1 microM, respectively. The apparent K(m) values in human liver microsomes, ranging from 6.9 to 8.6 microM, agreed well with these results. The method provides a sensitive tool for measuring extremely low UGT activities and a specific means for assessing interindividual differences in 1-hydroxypyrene-metabolizing UGT activities in human liver and other tissues.

Dimethyl Sulfoxide↗
PubMed2000

An outbreak of Listeria monocytogenes serotype 3a infections from butter in Finland.

In February 1999, an outbreak of listeriosis caused by Listeria monocytogenes serotype 3a occurred in Finland. All isolates were identical. The outbreak strain was first isolated in 1997 in dairy butter. This dairy began delivery to a tertiary care hospital (TCH) in June 1998. From June 1998 to April 1999, 25 case patients were identified (20 with sepsis, 4 with meningitis, and 1 with abscess; 6 patients died). Patients with the outbreak strain were more likely to have been admitted to the TCH than were patients with other strains of L. monocytogenes (60% vs. 8%; odds ratio, 17.3; 95% confidence interval, 2.8-136.8). Case patients admitted to the TCH had been hospitalized longer before cultures tested positive than had matched controls (median, 31 vs. 10 days; P=.008). An investigation found the outbreak strain in packaged butter served at the TCH and at the source dairy. Recall of the product ended the outbreak.

Adolescent↗
PubMed2000

Technical achievement: transthoracic Doppler echocardiography can be used to detect LAD restenosis after coronary angioplasty.

We investigated the capability of transthoracic Doppler echocardiography (TTE) to detect and quantify the severity of restenosis in the left anterior descending coronary artery (LAD) after percutaneous transluminal coronary angioplasty (PTCA). We studied 10 consecutive patients assigned for quantitative coronary angiography (qCA) due to a recurrent angina pectoris after PTCA of the LAD. The LAD was visualized by TTE, and the presence of local turbulence and an increase in the blood flow velocity was regarded to indicate coronary stenosis. To assess the severity of the stenosis, the increase of blood flow velocity was measured. Angiography showed stenoses of various degrees (27-100%) in all patients. All stenoses were detectable using TTE. Moreover, the ratio of maximal blood flow velocity at the site of stenosis to the pre-stenotic blood flow velocity (M/P-ratio) correlated significantly with the reduction of the luminal diameter of LAD (r = 0.85, P < 0.003). A M/P-ratio higher than 3.0 predicted a diameter reduction of 50% or higher with sensitivity and specificity of 100% in patients with a subtotal stenosis (n = 9). Our results indicate that stenoses in the LAD could be found and the severity of the stenoses could be quantified reliably with TTE. This approach is totally non-invasive and less expensive than coronary angiography and can be used clinically in clarifying restenosis after coronary angioplasty.

Aged↗
PubMed1999

Avidin is a promising tag for fusion proteins produced in baculovirus-infected insect cells.

The baculovirus expression vector system (BEVS) has become one of the most versatile and powerful eukaryotic systems for recombinant protein expression. We have constructed a novel baculovirus transfer vector (pbacAVs+C) which allows for the efficient production, detection, and single-step purification of the desired molecule as a secretion-compatible avidin fusion protein in insect cells. It also enables fast construction of the baculoviruses by site-specific transposition in Escherichia coli. To demonstrate the power of this vector, we report here on the production of immunologically intact hevein, a major cysteine-rich latex allergen, as avidin fusion protein. Our results indicate that avidin is a stable and versatile tag in the BEVS. It retains its extraordinarily high biotin-binding activity and also enables independent folding of the fusion partner. The versatility with which avidin fusion proteins can be detected, purified, and immobilized is the basis for the use of our system as a useful alternative in eukaryotic fusion protein production.

Amino Acid Sequence↗
PubMed1999

Enhanced morphine- and cocaine-induced behavioral sensitization in alcohol-preferring AA rats.

Locomotor stimulation and behavioral sensitization induced by acute and repeated treatment with alcohol, cocaine or morphine were studied in the alcohol-preferring AA (Alko, Alcohol), alcohol-avoiding ANA (Alko, Non-Alcohol) rats and non-selected Wistar rats. Daily treatment with alcohol (ethanol, 0.4 or 1.0 g/kg, IP) for 6 days had no effect on locomotor activity either in the AA or ANA rats. Acute cocaine (5, 10 or 20 mg/kg, IP) produced a locomotor stimulation in the animals of all lines studied, and there was no difference in this effect between the AA and ANA rats. During a 4-day repeated cocaine treatment, the AA rats became sensitized with the 10 mg/kg dose, while the ANA rats did not show any sensitization with this dose. With the 20 mg/kg cocaine dose, in addition to locomotor stimulation, the rats of all lines studied showed stereotyped behavior, which response was enhanced during repeated treatment. Morphine-induced locomotor stimulation was larger in the AA rats than in the ANA or Wistar rats both with 1.0 and 3.0 mg/kg doses and only the AA rats were sensitized during 4-day treatment with the 1 mg/kg dose. With the 3.0 mg/kg morphine dose, only the AA rats showed a weak sensitization evident only during the initial 30 min after morphine injection. As the drug-induced behavioral sensitization is an important factor in the development of drug addiction, it is possible that mechanisms underlying the enhanced susceptibility of the AA rats to morphine- and cocaine-induced sensitization contribute to the high intake of alcohol and other abused drugs by these animals.

Alcohol Drinking↗
PubMed1999

HMG CoA reductase inhibitors are related to improved systemic endothelial function in coronary artery disease.

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase (statins) may enhance vascular endothelial function independent of their cholesterol lowering effect. To test this hypothesis, we surveyed two groups of patients (age 55+/-7, mean+/-SD) with coronary artery disease that were matched for age, blood pressure and serum lipid levels. Group 1 comprised 23 men without lipid-lowering medication and Group 2 included 22 patients with ongoing HMG CoA reductase inhibitor medication. Flow-mediated (endothelium-dependent) arterial dilatation (FMD) and nitrate-mediated (smooth muscle dependent) dilatation (NMD) were measured in the brachial artery using high resolution ultrasound. FMD was considerably higher in group 2 (4.3+/-2.6 vs. 2.6+/-2.8%; P<0.05). In multivariate regression model, statin use was the only significant (P<0.05) predictor of FMD. In all subjects, FMD correlated with statin dose (P<0.05 for trend). NMD was non-significantly higher in group 2 (11.4+/-5.0 vs. 9.0+/-4.2%, P=0. 08). We conclude that patients with established coronary artery disease on HMG CoA reductase inhibitor therapy have better vascular endothelial function than similar patients without the medication. These data provide further support for the idea that HMG CoA reductase inhibitors enhance endothelial function independent of their lipid-lowering effects. This may suggest that these drugs could be beneficial in secondary prevention of coronary artery disease regardless of the serum cholesterol concentration.

Adult↗
PubMed1999

A novel wheat gliadin as a cause of exercise-induced anaphylaxis.

BACKGROUND: Food-dependent, exercise-induced anaphylaxis is a severe form of allergy; the reaction is caused by ingestion of a specific food before exercise. This disorder often escapes diagnosis because neither the ingested food nor the exercise alone induces the symptoms. OBJECTIVE: The aim of the study was to characterize the allergens involved in wheat-dependent, exercise-induced anaphylaxis and to describe the clinical outcome in a series of 18 adult patients. METHODS: All 18 patients had experienced recurrent episodes of generalized urticaria during exercise, 17 patients in association with collapse and 15 patients with an anaphylactic reaction. The symptoms appeared only when the patients had eaten food containing wheat before exercise. Wheat allergens were detected by immunoblotting, purified by gel filtration and reversed-phase chromatography, and subjected to N-terminal sequencing. The IgE-binding ability of the purified proteins was studied by ELISA, and their in vivo reactivity was studied by skin prick testing. RESULTS: IgE antibodies from pooled patient sera were bound to 65-kd and 40-kd wheat proteins in immunoblotting. The 65-kd allergen was a previously undescribed wheat protein, showing 61% sequence identity to gamma-gliadin, whereas the 40-kd allergen had 100% identity to alpha-gliadin. In ELISA, all 18 patients showed elevated IgE levels to the novel gamma-like gliadin, and 13 of the patients showed elevated IgE levels to the alpha-gliadin. None of the 54 control subjects with wheat allergy, urticaria, or coeliac disease had IgE antibodies to the gamma-like gliadin. The in vivo reactivity of the gamma-like gliadin was verified by positive skin prick test responses in all of the 15 patients who were tested. During the follow-up on a gluten-free or wheat-free diet, 3 patients experienced reactions after having unknowingly eaten wheat before exercise, but all the other patients who were adhering to the diet remained symptom-free. CONCLUSION: This study shows that wheat is a frequent cause of food-dependent, exercise-induced anaphylaxis and suggests that the major allergen is a previously undescribed gamma-like gliadin. For screening of this life-threatening allergy, we recommend skin prick testing with crude gliadin and we recommend a gluten-free diet for treatment.

Adolescent↗
PubMed1997

Seasonal increase in human IgE and IgG4 antisaliva antibodies to Aedes mosquito bites.

BACKGROUND: Mosquito bite-sensitive subjects frequently have circulating IgE and IgG4 antibodies to Aedes mosquito saliva proteins. METHODS: In the present study we examined the antibody response during a mosquito season in 14 subjects living in Finnish Lapland. Immunoblotting was performed with Aedes communis saliva and the 22- and 36-kD antisaliva antibody bands were analyzed. RESULTS: The preseason sera showed IgE antibodies to the main saliva antigens in 12, IgG4 antibodies in all 14 and IgG1 antibodies in 12 subjects, and the postseason sera in all but 1 subject. The postseason sera showed significantly more intense IgE (p < 0.05), IgG4 (p < 0.001) and IgG1 (p < 0.01) antibody bands than the preseason sera. CONCLUSION: These results show that seasonal exposure to mosquito bites leads to an increased IgE, IgG4 and IgG1 antibody response, a phenomenon similar to that occurring e.g. in pollen allergy.

Adult↗
PubMed1989

Quenching of fluorescence of pyrene-substituted lecithin by tetracyanoquinodimethane in liposomes.

In this work we have applied a kinetic scheme derived from fluorescence kinetics of pyrene-labeled phosphatidylcholine in phosphatidylcholine membrane to explain the fluorescence quenching of 1-palmitoyl-2-(10-[pyrenl-yl]-sn-glycerol-3-phosphatidylchol ine (PPDPC) liposomes by tetracyanoquinodimethane (TCNQ). The scheme was also found to be applicable to neat PPDPC and the effect of the quencher could be attributed to certain steps of the proposed mechanism. The TCNQ molecules influence the fluorescence of pyrene moieties in PPDPC liposome in two ways. Firstly, an interaction between the quencher molecule and the pyrene monomer in the excited state quenches monomer fluorescence and effectively prevents the diffusional formation of the excimer. Secondly, an interaction between the quencher molecule and the excited dimer quenches the excimer fluorescence. The TCNQ molecule does not prevent the formation of the excimer in pyrene moieties aggregated in such a way that they require only a small rotational motion to attain excimer configuration. The diffusional quenching rate constant is calculated to be 1.0 x 10(8) M-1 s-1 for the pyrene monomer quenching and 1.3 x 10(7) M-1 s-1 for the pyrene excimer quenching. The diffusion constant of TCNQ is 1.5 x 10(-7) cm2 s-1 for the interaction radii of 0.8-0.9 nm. The TCNQ molecules are practically totally partitioned in the membrane phase.

Diffusion↗
PubMed1988

Ca2+-induced lateral phase separation in phosphatidic acid/phosphatidylcholine monolayers as revealed by fluorescence microscopy.

Phase separation in mixed monolayers of phosphatidylcholine (PC) and pyrene-labeled phosphatidic acid (PA) was observed by fluorescence microscopy on an air/water interface as a function of subphase Ca2+ concentration and lateral packing pressure of the film. Below 45 mN m-1 and in the absence of Ca2+ no indications of phase immiscibility were observed. Addition of 1 mM Ca2+ caused extensive phase separation, which was evident immediately after spreading of the film. Further increase in Ca2+ concentration up to 30 mM increased the pyrene excimer intensity of the separated phosphatidic acid enriched domains. In the presence of Ca2+ (1-30 mM) and at surface pressures below 10 mN m-1 phase separation was always evident. However, as surface pressure exceeded 10 mN m-1, mixing of PC and PA occurred. Upon decompression of the film, phase separation reappeared at surface pressures close to 10 mN m-1. The surface textures of the film before and after the compression and subsequent relaxation were different. Inclusion of 30 mol% cholesterol increased the number and decreased the size of the PA domains. In films containing 50 mol% cholesterol no phase separation could be detected at the resolution available.

1,2-Dipalmitoylphosphatidylcholine↗