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Biomedical subjects

J Kallio

Publications and source records attributed to J Kallio.

At least 19 recordsLinked to original sources

Changes in the soleus muscle architecture after exhausting stretch-shortening cycle exercise in humans.

This study focused on the architectural changes in the muscle-tendon complex during the immediate and secondary (delayed) reductions of performance (bimodal recovery) caused by an exhaustive rebound type stretch-shortening cycle (SSC) exercise. The isometric plantar flexor torque during maximum voluntary contraction (MVC) was measured together with recording of electromyography (EMG) and ultrasonography from the soleus muscle before (BEF), after (AFT), 2 h (2H), 2 and 8 days (2D, 8D) after the SSC exercise (n=8). The performance variables (MVC torque and EMG activation) followed the bimodal recovery patterns. This was not the case in the changes of the fascicle length and muscle thickness. The relative torque changes in MVC correlated positively (R=0.78, P=0.02) to the corresponding averaged EMG changes between BEF and 2H (BEF-->2H); the significance disappeared in the comparison between 2H and 2D (2H-->2D), during which period MVC showed a secondary reduction. The relative torque changes in MVC showed no correlation with the changes in muscle thickness between BEF-2H. However, this correlation between 2H-2D was negative (R=-0.85, P<0.01). The fascicle shortening/average EMG ratio in MVC increased at 2H, and then decreased more at 2D than 2H (P<0.05). Thus, the secondary performance decline was not related to the corresponding EMG reduction but to the increased muscle thickness, which peaked at 2D. The results suggest clearly that the secondary decline in MVC could be related to the increase in muscle volume.

Adult↗

The Leu7Pro polymorphism of neuropeptide Y is associated with younger age of onset of type 2 diabetes mellitus and increased risk for nephropathy in subjects with diabetic retinopathy.

Several studies have shown genetic predisposition for diabetic complications. The leucine7 to proline7 (Leu7Pro) polymorphism of preproNPY has been shown to be a risk factor for diabetic retinopathy in type 1 diabetes. In the current study we examined the contribution of this polymorphism on the progression of retinopathy in Caucasian type 1 and type 2 diabetes patients. Patients with type 2 diabetes and the Leu7Pro polymorphism developed retinopathy at younger age because of markedly earlier disease onset of diabetes (RC- 6.8, 95% CI-12.2 - [- 1.5]), but no association of the Leu7Pro polymorphism with the current severity of retinopathy was detected. A strong association of the polymorphism with proteinuria in type 2 diabetes patients with retinopathy could be detected (OR 3.1, 95% CI 1.1-8.8); 31% of subjects having both retinopathy and proteinuria had the polymorphism compared to only 13% of retinopathy patents without concomitant proteinuria (p = 0.032). Plasma concentrations of NPY were increased in subjects with proteinuria (79.2+/-28.4 and 64.7+/-26.2 pmol/l, p = 0.001). These results suggest that the Leu7Pro polymorphism could be used to predict earlier onset of type 2 diabetes and retinopathy, and increased risk for diabetic nephropathy.

Adult↗

The effects of muscle history on short latency stretch reflex response of soleus muscle.

The purpose of the present study was to investigate the combined effects of muscle history, activation and stretching velocity on short latency stretch response (SLR). Stretches (70, 120 and 200 deg s-1) were elicited to both passive and active (10-25% MVC) triceps surae muscle with constant (ISO), lengthened (LEN) or shortened (SHO) muscle length. Under the passive SHO pre-condition both SLR amplitude and reflex torque (RT) decreased where as latency increased compared with the passive ISO pre-condition. Such observations were absent in active trials. Stretches applied to a lengthening passive muscle (LEN) resulted in smaller SLR amplitude and RT compared with passive ISO. In active muscle the stretch response increased with stretching velocity in ISO and SHO. However, in LEN there was large interindividual variability and no velocity dependent increase in SLR amplitude was observed. Smaller amplitude and longer latency of passive SLR in SHO could result from increased slack in the intrafusal fibres, which may be compensated by fusimotor activation during the active condition. The mechanism behind the smaller amplitude in passive LEN and the lack of velocity dependence in active LEN may be related to changes in motoneuron pool excitability or changes in the spindle sensitivity to stretch.

Adaptation, Physiological↗

Enhancing biological phosphorus removal from municipal wastewater with partial simultaneous precipitation.

Pilot-scale tests to enhance phosphorus removal with ferrous sulphate in a biological phosphorus and nitrogen removal process (modified UCT) for treating municipal wastewater were performed. The results indicated that Fe(II) competes with the BioP organisms and will inhibit the biological phosphorus removal process completely at doses exceeding 9 g m(-3) of Fe(II). The goal of an effluent P level of 0.5 mg l(-1) can be attained with 5 g m(-3) of Fe(II). A consistent effluent concentration of 0.3 mg l(-1) could not be achieved with this method. A centrifugation method to evaluate the dewatering properties of sludge was developed. Comparison of the settling and dewatering properties between activated sludge from the pilot plant and a full-scale simultaneous precipitation process indicated no consistent differences between them. The poor settling properties are due to the long sludge retention time needed by nitrification and not to the biological phosphorus removal process.

Bioreactors↗

The mismatch negativity as an index of temporal processing in audition.

OBJECTIVES: The relation of the mismatch negativity (MMN) elicitation with behavioral stimulus discrimination as well as the replicability of the MMN was evaluated for intervals between paired tones. METHODS: The MMN, obtained in a passive oddball paradigm in two sessions separated by 4-21 days and behavioral responses (button presses to target stimuli) in a separate session were recorded from 10 adult healthy subjects. The standard stimulus (P=0.79) was a tone pair separated by a 120 ms silent inter-stimulus interval (ISI) and the deviant stimuli were tone pairs with an ISI of 100, 60, and 20 ms (P=0.07 for each). RESULTS: The 20 and 60 ms ISI deviant tone pairs elicited a significant MMN during both recording sessions and they were also behaviorally discriminated, whereas neither did the 100 ms ISI deviant pair elicit significant MMN nor was it behaviorally discriminated. Furthermore, there was a significant correlation between the MMN and reaction times to the 20 and 60 ms ISI deviant pairs. The 20 ms ISI deviant stimulus elicited highly replicable MMNs (r=0.75), whereas the less well discriminated 60 ms ISI deviant pair did not (r=0.60). CONCLUSIONS: The MMN reflects discrimination accuracy of temporal sound intervals. Furthermore, when the physical difference between the standard and deviant tone pair in the temporal domain is large, it is elicited with high reliability.

Adult↗

cDNA cloning, expression studies and chromosome mapping of human type I serine/threonine kinase receptor ALK7 (ACVR1C).

Transforming growth factor-beta (TGF-beta) superfamily related growth factors signal by binding to transmembrane type I and type II receptor serine/threonine kinases (RSTK), which phosphorylate intracellular Smad transcription factors in response to ligand binding. Here we describe the cloning of the human type I RSTK activin receptor-like kinase 7 (ALK7), an orthologue of the previously identified rat ALK7. Nodal, a TGF-beta member expressed during embryonic development and implicated in developmental events like mesoderm formation and left-right axis specification, was recently shown to signal through ALK7. We found ALK7 mRNA to be most abundantly expressed in human brain, pancreas and colon. A cDNA encoding the open reading frame of ALK7 was obtained from a human brain cDNA library. Furthermore, a P1 artificial chromosome (PAC) clone containing the human ALK7 gene was isolated and fluorescent in situ hybridization (FISH) on metaphase chromosomes identified the gene locus as chromosome 2q24.1-->q3. To test the functionality of the ALK7 signaling, we generated recombinant adenoviruses containing a constitutively active form of ALK7 (Ad-caALK7), which is capable of activating downstream targets in a ligand independent manner. Infection with Ad-caALK7 of MIN6 insulinoma cells, in which ALK7 has previously been shown to be endogenously expressed, led to a marked increase in the phosphorylation of Smad2, a signaling molecule also used by TGF-betas and activins.

Activin Receptors, Type I↗

Enhanced exercise-induced GH secretion in subjects with Pro7 substitution in the prepro-NPY.

The leucine 7 to proline 7 (Leu7Pro) polymorphism in the signal peptide of NPY is associated with high blood lipid concentrations and accelerated rate of atherosclerosis as well as diabetic retinopathy. Also, healthy subjects with this polymorphism have increased NPY secretion during sympathetic stimulation. Because NPY may regulate GH release and ghrelin may regulate NPY formation, we studied the effects of the Leu7/Pro7 genotype on GH, ghrelin, and IGF-I secretion during standardized cycle-ergometer exercise. Furthermore, we studied the effect of the Leu7/Pro7 genotype on diurnal GH secretion in rest in a separate study. The subjects with Leu7/Pro7 genotype had 54% higher maximal increases in the plasma GH concentrations than the controls during exercise. There were no significant differences in the ghrelin or IGF-I concentrations during exercise among the groups. Furthermore, there were no differences in diurnal GH secretion between the genotypes. The results indicate that the prepro-NPY genotype has an influence on GH response during exercise in humans. The clinical significance of this finding is not known, and further studies are needed to evaluate whether the observed change in GH secretion during exercise could play a role in promoting diseases.

Adult↗

The dilemma of suspicious urine cytology in patients being followed for bladder cancer.

BACKGROUND AND AIMS: Urine cytology is gold standard for clinical tests used in the diagnosis and follow-up of bladder cancer. Cytology, however, exhibits variable sensitivity depending on tumour grade and interpretation of urine specimens is highly dependent on the skill of the examiner. Furthermore, a "suspicious" cytology report (class III) makes clinicians uncomfortable. In these cases, a more objective test, such as the BTA stat Test, may be useful in providing clarification. The aim of this study was to evaluate the dilemma of suspicious routine urine cytology and to determine whether the BTA stat Test provides diagnostic aid in this rare but controversial category. MATERIAL AND METHODS: 506 consecutive patients who were being followed for bladder cancer were included in the study. A voided urine sample was obtained prior to routine follow-up cystoscopy and split for culture and testing with the BTA stat Test. Clinical status of the disease was evaluated in patients with suspicious urine cytology, and the diagnostic aid of the BTA stat Test in these patients was determined. RESULTS: A total of 57 patients (11.3%) had urine cytology classified as suspicious. The BTA stat Test was positive in 29 (50.9%) and negative in 28 (49.1%) patients. Nineteen (33.3%) patients had recurrence at routine cystoscopy. Of the remaining 38 patients, 10 were further investigated due to a positive BTA stat Test. Two additional recurrences were detected bringing the total number of recurrences to 21 (36.8%), 48.3% (14/29) of the patients with positive and 25.0% (7/28) of the patients with negative BTA stat Test had recurrence (p = 0.069). Overall, 65.5% (19/29) of the patients with a positive BTA stat Test were found to have recurrence either at routine cystoscopy, at further investigations, or at the next cystoscopy compared to that of 35.7% (19/28) in those with negative testing (p = 0.024). The overall sensitivity of the BTA stat Test was 66.7%, and the specificity was 58.3%. CONCLUSIONS: At least a third of the patients under follow-up for bladder cancer with suspicious cytology had a recurrence, indicating that these patients are a risk group for recurrence. More importantly, a BTA stat Test result seems to provide some help in distinguishing those patients with very high risk for recurrence, for whom invasive further investigations should be conducted and a close follow-up policy maintained.

Aged↗

Influence of hydroxychloroquine on the bioavailability of oral metoprolol.

AIMS: Hydroxychloroquine (HCQ) is used widely in the treatment of chronic inflammatory diseases such as rheumatoid arthritis. Since there is great interindividual variability in the pharmacokinetics of HCQ and chloroquine is a potent inhibitor of CYP2D6-catalysed pathways in vitro, we wished to study the interaction of HCQ with CYP2D6-mediated metabolism of other drugs in vivo. METHODS: Metoprolol and dextromethorphan (DM) were selected as probe drugs because they are well-studied and widely used test substrates of CYP2D6. In this randomized, double-blind crossover study, seven healthy volunteers with extensive metabolizer phenotype for CYP2D6 ingested either 400 mg hydroxychloroquine or placebo daily for 8 days after which single oral dose pharmacokinetics of metoprolol were investigated. Dextromethorphan metabolic ratio (DM-MR) was also determined at baseline and after the ingestion of HCQ or placebo. RESULTS: Concomitant administration of HCQ increased the bioavailability of metoprolol, as indicated by significant increases in the area under the plasma concentration-time curve (65 +/- 4.6%) and maximal plasma concentrations (72 +/- 6.9%) of metoprolol. While the DM-MR values were not significantly changed, the phenotypic classification of one individual, who was heterozygous for a mutant CYP2D6 allele, was converted to a poor metabolizer by HCQ administration. CONCLUSIONS: HCQ inhibits metoprolol metabolism most probably by inhibiting its biotransformation by CYP2D6. The inhibitory effect of HCQ on dextromethorphan metabolism was not apparent when DM-MR was used as an indicator, except in an individual with limited CYP2D6 capacity.

Adrenergic beta-Antagonists↗

Antenatal and early postnatal dexamethasone treatment decreases cortisol secretion in preterm infants.

Glucocorticoids are used antenatally to accelerate the maturation of fetal respiratory and cardiovascular systems when a threat of preterm delivery exists. Postnatally, they are used to prevent and treat respiratory distress syndrome. This study investigates the effects of antenatal (ACT) and early postnatal corticosteroid treatment (PCT) on serum cortisol and plasma catecholamine and adenosine 3',5'-cyclic monophosphate (cAMP) concentrations in preterm neonates. The infants in the ACT group had a significantly lower cortisol concentration than the infants in the non-ACT group on the first day of life. After birth, the infants were further divided into non-PCT and PCT groups. PCT suppressed cortisol levels significantly after 2 days, and the cortisol levels were still lower 2 days after discontinuation of PCT. No effect of PCT on plasma cAMP or catecholamine concentrations was observed. The results indicate that both ACT and a short PCT can significantly suppress basal cortisol levels in preterm infants.

Catecholamines↗

Adrenocorticotropin and corticotropin-releasing hormone tests in preterm infants.

The short ACTH test is used in evaluating the hypothalamo-pituitary-adrenal axis (HPA-axis) in preterm neonates after dexamethasone treatment. This test mainly examines primary adrenal suppression but is also used as a method to test secondary adrenal insufficiency because long-term deprivation of ACTH causes atrophy of the adrenal cortex. The CRH test, on the other hand, directly examines the function of the pituitary. We tested 18 infants in the neonatal intensive care unit with both the ACTH test and the CRH test to determine which of these two tests more reliably demonstrates HPA-axis suppression. One patient had normal responses both in the ACTH test and in the CRH test when the limit of 360 nmol/L was used as a sign of proper cortisol secretion. In four cases the patients' cortisol secretion would have been regarded as normal by the low-dose ACTH test, whereas the CRH test did not show an adequate cortisol response. In conclusion, the ACTH test did not reliably indicate HPA-axis suppression after a short (<2 weeks) course of dexamethasone therapy in this study. Therefore, whether the infant is or will be under acute stress after short glucocorticoid treatment, ensuring adequate cortisol secretion with the CRH test should be considered.

Adrenal Gland Diseases↗

Basic auditory dysfunction in dyslexia as demonstrated by brain activity measurements.

Although the generality of dyslexia and its devastating effects on the individual's life are widely acknowledged, its precursors and associated neural mechanisms are poorly understood. One of the two major competing views maintains that dyslexia is based primarily on a deficit in linguistic processing, whereas the other view suggests a more general processing deficit, one involving the perception of temporal information. Here we present evidence in favor of the latter view by showing that the neural discrimination of temporal information within complex tone patterns fails in dyslexic adults. This failure can be traced to early cortical mechanisms that process auditory information independently of attention.

Adult↗

Weekly mitomycin C followed by monthly bacillus Calmette-Guerin or alternating monthly interferon-alpha2B and bacillus Calmette-Guerin for prophylaxis of recurrent papillary superficial bladder carcinoma.

PURPOSE: We evaluated alternatives to bacillus Calmette-Guerin (BCG) monotherapy using a new combination of chemotherapy and immunotherapy for recurrent superficial bladder carcinoma. MATERIALS AND METHODS: A total of 236 patients with frequently recurrent stage Ta or T1 bladder tumors were enrolled in our prospective, randomized, multicenter Finnbladder IV study. The initial mitomycin C instillation was instilled in all patients perioperatively after transurethral resection, followed by 4 weekly instillations of mitomycin C. Thereafter patients were randomized to receive monthly for up to 1 year BCG only or interferon-alpha2b and BCG alternating monthly. Primary end points were time to initial recurrence, recurrence rate (number of recurrences per patient-year) and recurrence index (number of recurrent tumors per patient-year). RESULTS: Of the 236 randomized patients 205 were eligible for study with a median overall followup of 30.7 months. Monthly BCG was superior to alternating monthly interferon-alpha and/or BCG with respect to time to initial recurrence (log rank test p <0.00001) as well as recurrence rate (0.4 versus 0.9, p <0.00001) and index (0.9 versus 3.0, p <0.00001). Side effects were limited. CONCLUSIONS: Monthly BCG given for up to 1 year preceded by perioperative and an additional 4 weekly mitomycin C instillations is a well tolerated mode of instillation therapy, providing excellent tumor control comparable to that of the best reported instillation regimens. No benefit was obtained by alternating interferon-alpha2b with BCG.

Adjuvants, Immunologic↗

Receptor subtype-induced targeting and subtype-specific internalization of human alpha(2)-adrenoceptors in PC12 cells.

The three alpha(2)-adrenergic receptor subtypes have distinct tissue distributions, desensitization properties, and, in some cell types, subtype-specific subcellular localization and trafficking properties. The subtypes also differ in their neuronal physiology. Therefore, we have investigated the localization and targeting of human alpha(2)-adrenoceptors (alpha(2)-AR) in PC12 cells, which were transfected to express the alpha(2)-AR subtypes A, B, and C. Inspection of the receptors by indirect immunofluorescence and confocal microscopy showed that alpha(2A)-AR were mainly targeted to the tips of the neurites, alpha(2B)-AR were evenly distributed in the plasma membrane, and alpha(2C)-AR were mostly located in an intracellular perinuclear compartment. After agonist treatment, alpha(2A)- and alpha(2B)-AR were internalized into partly overlapping populations of intracellular vesicles. Receptor subtype-specific changes in PC12 cell morphology were also discovered: expression of alpha(2A)-AR, but not of alpha(2B)- or alpha(2C)-AR, induced differentiation-like changes in cells not treated with NGF. Also alpha(2B)-AR were targeted to the tips of neurites when they were coexpressed in the same cells with alpha(2A)-AR, indicating that the targeting of receptors to the tips of neurites is a consequence of a change in PC12 cell membrane protein trafficking that the alpha(2A)-subtype induces. The marked agonist-induced internalization of alpha(2A)-AR observed in both nondifferentiated and differentiated PC12 cells contrasts with earlier results from non-neuronal cells and points out the importance of the cellular environment for receptor endocytosis and trafficking. The targeting of alpha(2A)-AR to nerve terminals in PC12 cells is in line with the putative physiological role of this receptor subtype as a presynaptic autoreceptor.

Adrenergic alpha-Antagonists↗

Chloroethylclonidine and 2-aminoethyl methanethiosulfonate recognize two different conformations of the human alpha(2A)-adrenergic receptor.

The substituted cysteine-accessibility method and two sulfhydryl-specific reagents, the methane-thiosulfonate derivative 2-aminoethyl methanethiosulfonate (MTSEA) and the alpha(2)-adrenergic receptor (alpha(2)-AR) agonist chloroethylclonidine (CEC), were used to determine the relative accessibility of engineered cysteines in the fifth transmembrane domain of the human alpha(2A)-AR (Halpha2A). The second-order rate constants for the reaction of the receptor with MTSEA and CEC were determined with the wild type Halpha2A (cysteine at position 201) and receptor mutants containing accessible cysteines at other positions within the binding-site crevice (positions 197, 200, and 204). The rate of reaction of CEC was similar to that of MTSEA at residues Cys-197, Cys-201, and Cys-204. The rate of reaction of CEC with Cys-200, however, was more than 5 times that of MTSEA, suggesting that these compounds may interact with two different receptor conformations. MTSEA, having no recognition specificity for the receptor, likely reacts with the predominant inactive receptor conformation (R), whereas the agonist CEC may stabilize and react preferentially with the active receptor conformation (R*). This hypothesis was consistent with three-dimensional receptor-ligand models, which further suggest that alpha(2A)-AR activation may involve the clockwise rotation of transmembrane domain 5.

Adrenergic alpha-Antagonists↗

Timing of peak serum cortisol values in preterm infants in low-dose and the standard ACTH tests.

The low-dose ACTH test seems to reveal mild cases of adrenal insufficiency and is beginning to be preferred over the standard ACTH test in the evaluation of adrenal suppression both in infants and in adults. The concentration-time profile of plasma cortisol in infants after a low ACTH dose is obscure. In this crossover study, we compared timing of the peak values in the low-dose and the standard ACTH stimulation tests in preterm and full-term infants. We performed the standard ACTH tests (250 microg/1.73 m2) and the low-dose ACTH tests (1 microg/1.73 m2) on 10 infants (26-40 wk gestational age) and measured serum cortisol concentration at 0, 30, 40, 60, and 120 min by RIA. Nine of the infants had received postnatal glucocorticoid treatment, and most of them had also been treated with dexamethasone antenatally. In the low-dose test, the peak values occurred at 30 or 40 min in 9/10 patients. In the standard-dose test, the peak values occurred at 60 or 120 min in 8/10 patients. These results are comparable with those from adults. According to this study, blood samples for the low-dose ACTH test in infants should be taken before dosing and between 30 and 40 min after dosing.

Adult↗