Showing papers by "University of Turku published in 1989"

Microbial amylolytic enzymes

Abstract: Starch-degrading, amylolytic enzymes are widely distributed among microbes. Several activities are required to hydrolyze starch to its glucose units. These enzymes include alpha-amylase, beta-amylase, glucoamylase, alpha-glucosidase, pullulan-degrading enzymes, exoacting enzymes yielding alpha-type endproducts, and cyclodextrin glycosyltransferase. Properties of these enzymes vary and are somewhat linked to the environmental circumstances of the producing organisms. Features of the enzymes, their action patterns, physicochemical properties, occurrence, genetics, and results obtained from cloning of the genes are described. Among all the amylolytic enzymes, the genetics of alpha-amylase in Bacillus subtilis are best known. Alpha-Amylase production in B. subtilis is regulated by several genetic elements, many of which have synergistic effects. Genes encoding enzymes from all the amylolytic enzyme groups dealt with here have been cloned, and the sequences have been found to contain some highly conserved regions thought to be essential for their action and/or structure. Glucoamylase appears usually in several forms, which seem to be the results of a variety of mechanisms, including heterogeneous glycosylation, limited proteolysis, multiple modes of mRNA splicing, and the presence of several structural genes.

Dementia in Parkinson's disease is related to neuronal loss in the medial substantia nigra.

Abstract: Regional neuronal loss in the substantia nigra was studied in relation to extrapyramidal symptoms and dementia in 12 patients with idiopathic Parkinson's disease (PD) and in 18 control subjects. Four areas of the right substantia nigra were investigated at the level of the superior colliculus and caudal red nucleus. In Parkinson's disease, the percentages of neurons, from the medial to the lateral part of the substantia nigra, were reduced to 49%, 31%, 41%, and 25% of the control values. The number of neurons in the lateral part showed a negative correlation with the severity of rigidity and hypokinesia, whereas tremor was less noticeable in patients with few neurons. The degree of dementia of the patients had a significant correlation only with neuronal loss in the medial part of the substantia nigra, suggesting, in view of the topographical organization of the neurons in the substantia nigra, that intact projections to the caudate nucleus and limbic and cortical areas are a prerequisite for normal cognitive functioning and that their dysfunction leads to clinical dementia.

Effects of dexmedetomidine, a selective α2‐adrenoceptor agonist, on hemodynamic control mechanisms

Abstract: Dexmedetomidine, a selective alpha 2-adrenoceptor agonist, was administered to five healthy male volunteers in single intravenous doses of 12.5, 25, 50, and 75 micrograms as part of a placebo-controlled study. The drug caused dose-dependent decreases in systolic and diastolic blood pressure. A small initial hypertensive response was observed after injection of the two highest doses. Heart rate was decreased. The concentration of norepinephrine in plasma was decreased significantly (by up to 92%), and the decrease was dose-dependent. No significant drug-induced alterations were observed in plasma renin activity or in the concentrations of atrial natriuretic peptide and arginine vasopressin in plasma. Other drug effects included dose-dependent impairment of vigilance and stimulation of growth hormone secretion. Plasma cortisol levels were unaffected. Dexmedetomidine is a potentially useful tool for studies of the physiology and pharmacology of alpha 2-adrenoceptors in human beings and may have therapeutic applications in clinical conditions in which sedative and sympatholytic effects are considered beneficial, such as premedication for anesthesia and surgery.

Polymerase chain reaction for human picornaviruses.

Abstract: We have used enzymic amplification of specific nucleic acid sequences followed by hybridization, for the rapid detection and typing of human picornaviruses after cell culture isolation The test is based on the synthesis of cDNA, the polymerase chain reaction and the use of oligonucleotide probes The primers were selected from the 5' non-coding region of the genome representing highly conserved regions Sequences specific to enteroviruses and rhinoviruses were used as probes The assay was able to identify all the picornavirus reference strains analysed and it was also possible to discriminate between enteroviruses and rhinoviruses by the hybridization procedure When 29 picornavirus clinical isolates were analysed, all except one were detected by gel electrophoresis and a specific hybridization signal was obtained with all except three strains using the oligonucleotide probes

Pharmacokinetic Implications for the Clinical Use of Propofol

Abstract: Propofol, the recently marketed intravenous induction agent for anaesthesia, is chemically unrelated to earlier anaesthetic drugs. This highly lipophilic agent has a fast onset and short, predictable duration of action due to its rapid penetration of the blood-brain barrier and distribution to the CNS, followed by redistribution to inactive tissue depots such as muscle and fat. On the basis of pharmacokinetic-pharmacodynamic modelling, a mean blood-brain equilibration half-life of only 2.9 minutes has been calculated. In most studies, the blood concentration curve of propofol has been best fitted to a 3-compartment open model, although in some patients only 2 exponential phases can be defined. The first exponential phase half-life of 2 to 3 minutes mirrors the rapid onset of action, the second (34 to 56 minutes) that of the high metabolic clearance, whereas the long third exponential phase half-life of 184 to 480 minutes describes the slow elimination of a small proportion of the drug remaining in poorly perfused tissues. Thus, after both a single intravenous injection and a continuous intravenous infusion, the blood concentrations rapidly decrease below those necessary to maintain sleep (around 1 mg/L), based on both the rapid distribution, redistribution and metabolism during the first and second exponential phases (more than 70% of the drug is eliminated during these 2 phases). During long term intravenous infusions cumulative drug concentrations and effects might be expected, but even then the recovery times do not appear to be much delayed. The liver is probably the main eliminating organ, and renal clearance appears to play little part in the total clearance of propofol. On the other hand, because the total body clearance may exceed liver blood flow, an extrahepatic metabolism or extrarenal elimination (e.g. via the lungs) has been suggested. Approximately 60% of a radiolabelled dose of propofol is excreted in the urine as 1- and 4-glucuronide and 4-sulphate conjugates of 2.6-diisopropyl 1,4-quinol, and the remainder consists of the propofol glucuronide. Thus for hepatic and renal diseases, co-medication, surgical procedure, gender and obesity do not appear to cause clinically significant changes in the pharmacokinetic profile of propofol, but the decrease in the clearance value in the elderly might produce higher concentrations during a long term infusion, with an increased drug effect. In addition, the lower induction dose observed in relation to increased age might be partly explained by a smaller central volume of distribution.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of the yopA gene encoding the Yop1 virulence determinants of Yersinia spp.

Abstract: The Yop proteins of Yersinia are important virulence determinants. The Yop1 protein sequences of Yersinia pestis, Yersinia pseudotuberculosis, and two Yersinia enterocolitica serotypes, 0:3 and 0:8, deduced from the nucleotide sequences of the corresponding yopA genes, were compared. Most differences were found in the hydrophilic domains of the proteins, whereas the hydrophobic domains were conserved. The amino acid sequences revealed a signal sequence 25 amino acids long. No cysteine residues were present, even though Yop1 forms a polymeric structure. The transcription startpoint of yopA was determined by primer extension. The coding region and transcription startpoint were separated by a leader sequence 270 nucleotides long. The yopA promoter sequence of Y.pestis is identical to the corresponding sequence of Y. pseudotuberculosis and transcription studies revealed that this promoter is active in Y.pestis. Thus, the inability of Y.pestis to express the Yop1 protein is due to a single base pair deletion in the coding region of the yopA gene of Y.pestis.

The cold pressor test: effects on sympathetic nerve activity in human muscle and skin nerve fascicles

Abstract: Micro-electrode multi-unit recordings of muscle nerve sympathetic activity (MSA) involved in cardiovascular homeostasis or skin nerve sympathetic activity (SSA) involved in thermoregulation were made in the right peroneal nerve of 48 healthy volunteers during performance of the cold pressor test, i.e. immersion of one hand in ice water (2 +/- 0.5 degrees C) for 1 min. Eleven subjects underwent the same procedure on a second MSA recording occasion. As a rule, immersion evoked an increase in MSA, with a gradual decrease on emersion. The response showed a wide range of variation between and within subjects; the intra-individual difference between first and second immersion on the same recording occasion was up to sevenfold, and from first to second recording up to fivefold. The increase in MSA correlated with the degree of discomfort from the ice water. In nine subjects with a large increase in MSA on ice water immersion, intracutaneous painful electrical stimulation to a level equalling the discomfort from the ice water was added, but it was not accompanied by any change in MSA. The increase in MSA was accompanied by and correlated quite well with an increase in blood pressure. Intra-arterial blood pressure recordings showed that MSA occurred at pressure levels normally associated with total inhibition of MSA, and that an inverse linear relationship between diastolic blood pressure and MSA at rest was abolished during the ice water immersion. SSA showed no consistent change with ice water immersion. It is concluded that the cold pressor test is a powerful activator of MSA, i.e. baroreceptor-governed vasoconstrictor outflow; that MSA contributes to the blood pressure elevation with this manoeuvre; that MSA operates at another blood pressure level during the manoeuvre and that the baroreflex inhibitory level consequently is changed; and that the response is not a reaction to pain only.

Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema. Relationship between plasma essential fatty acid changes and clinical response.

Abstract: Gamma-linolenic acid in the form of a particular variety of evening primrose oil (Epogam) has been reported of value in the treatment of atopic eczema. Nine controlled trials of evening primrose oil were performed in eight centres. Four of the trials were parallel and five cross-over. Doctors and patients assessed the severity of eczema by scoring measures of inflammation, dryness, scaliness, pruritus and overall skin involvement. Individual symptom scores were combined to give a single global score at each assessment point. In the analysis of the parallel studies, both patient and doctor scores showed a highly significant improvement over baseline (P less than 0.0001) due to Epogam: for both scores the effect of Epogam was significantly better than placebo. Similar results were obtained on analysis of the cross-over trials, but in this case the difference between Epogam and placebo in the doctors' global score, although in favour of Epogam, failed to reach significance. The effects on itch were particularly striking. There was no placebo response to this symptom, whereas there was a substantial and highly significant response to Epogam (P less than 0.0001). When the improvements, or otherwise, in clinical condition were related to changes in plasma levels of dihomogammalinolenic and arachidoni acids, it was found that there was a positive correlation between an improvement in clinical score and a rise in the fatty acid levels.

Patellofemoral relationships in recurrent patellar dislocation.

Abstract: Magnetic resonance imaging was used to analyse the patellofemoral relationships during the first 30 degrees of knee flexion in women with recurrent patellar dislocation. The patellofemoral joints were imaged both sagittally and axially with the knee flexed 0 degrees, 10 degrees, 20 degrees, and 30 degrees. At the beginning of knee flexion the sulcus angle was greater than in unaffected women, the lateral patellofemoral angle was smaller, the patella displaced further laterally, tilted more laterally and the congruence angle was directed more laterally. At 30 degrees of knee flexion these differences were less marked than at 0 degree to 10 degrees. Logistic regression analysis showed that the sulcus angle at 10 degrees of knee flexion was the most diagnostic feature, indicating that there is an anatomical predisposition to recurrent dislocation and that pathological patellar tracking starts from the beginning of flexion. Traditional sunrise radiographic films taken at 25 degrees to 30 degrees knee flexion clearly miss diagnostically important information.

Stage-specific expression of nucleoprotein mRNAs during rat and mouse spermiogenesis.

Abstract: The expression of mRNAs for a transition protein (TP1) and two variants of protamines (P1 and P2) during rat and mouse spermiogenesis was investigated using cDNA hybridization techniques. Slot-blot analyses from 1-mm segments of seminiferous tubules and in situ hybridization from testis sections showed that the levels of mRNA for TP1 increased in step-7 round spermatids at substage VIIb of the seminiferous epithelial cycle, earlier than that of P1 and P2 at substage VIIc. The mRNA levels of all transcripts remained high during steps 8-13 in both species. In the rat, the mRNA of TP1 disappeared during step 14 between substages XIVa and XIVb. The P1 mRNA levels decreased during steps 15-16 (stages I-III) and the P2 mRNA during step 15 (stage I). In the mouse, TP1 mRNA disappeared during step 13 (stage I). The P1 mRNA level decreased before P2 in step 14 (stage II), whereas P2 was detected up to step 15 (stage V). Northern-blot analyses with all three cDNA probes revealed two sizes of mRNA and their stage-specific expression. The shorter transcripts appeared later than the longer ones, at the steps of spermiogenesis where translation is known to begin. The results suggest that transcription of TP1, P1, and P2 mRNAs starts at specifically defined times during spermiogenesis and that the temporal translational regulation of these mRNAs is different.

Lisuride, a dopamine agonist in the treatment of early Parkinson's disease.

Abstract: A randomized, prospective trial in 90 de novo parkinsonian patients showed that 4 years9 treatment with lisuride resulted in significantly fewer end-of-dose disturbances and peak-dose dyskinesias, but also less improvement in parkinsonian disability, than with levodopa. Early combination of lisuride and a low dose of levodopa, during a 4-year follow-up, resulted in a therapeutic response equal to that achieved with high-dose levodopa alone, but significantly fewer end-of-dose failures and dyskinesias. Thus it seems advisable that treatment should begin in the early phase of the disease with a dopamine agonist such as lisuride combined with a low dose of levodopa.

Medetomidine — a novel α2-adrenoceptor agonist: A review of its pharmacodynamic effects

Abstract: 1. The pharmacodynamic effects of medetomidine, a novel alpha 2-adrenoceptor agonist, are reviewed. 2. In receptor binding experiments, and in isolated organ preparations medetomidine shows high specificity and selectivity to alpha 2-adrenoceptors. Its alpha 2/alpha 1 selectivity ratio is 1620 compared to 220 of clonidine. It is a highly potent full agonist at alpha 2-adrenoceptors, a fact that also distinguishes it from clonidine. 3. Medetomidine induces a dose-dependent decrease in the central release and turnover of norepinephrine (NE) measured as changes in metabolite concentrations or using pharmacological intervention techniques. 4. The selectivity, specificity and potency of medetomidine is further supported by various in vivo experiments showing dose-dependent hypotensive, bradycardic, sedative, anxiolytic mydriatic, hypothermic and analgesic effects. 5. The pharmacological, neurochemical and behavioral effects of medetomidine can be inhibited by prior, simultaneous or subsequent administration of selective and specific alpha 2-antagonists. 6. In humans medetomidine is well-tolerated and pharmacodynamic effects including e.g. dose-dependent decrease of vigilance, blood pressure, heart rate, salivary secretion and plasma NE are compatible with an agonistic action at alpha 2-adrenoceptors.

Carotid arteriosclerosis in identical twins discordant for cigarette smoking.

Abstract: From a nationwide twin panel, identical twin pairs with highest discordance in cigarette smoking were selected for a study of arteriosclerosis (49 pairs with a mean age of 52 years). Smoking history was obtained in 1975, 1981, and 1986. The mean life-long smoking dose of the smoking cotwins was 20 package-years. The smoking and nonsmoking cotwins had similar systolic and diastolic blood pressures, total plasma cholesterol level, body mass index, and some psychosocial factors; the only difference was found in use of alcohol, which was greater among smoking cotwins. Duplex sonography of carotid arteries was performed. Carotid artery stenoses (narrowing of area of the lumen with 15-60%) were found in nine pairs: in nine smoking twins and in two of their nonsmoking cotwins (p = 0.036). The total area of carotid plaques was 3.2 times larger in smoking cotwins (p less than 0.001). The thickness of the inner layer of carotid arteries was more marked in smoking cotwins (p less than 0.001). The size of plaques and the degree of inner layer thickening correlated with the dose of smoking (NS). The association of smoking with carotid arteriosclerosis was highly significant even after the adjustment for age, total plasma cholesterol level, diastolic blood pressure, and body mass index in multiple logistic regression analyses.

Pharyngitis in Adults: The Presence and Coexistence of Viruses and Bacterial Organisms

Abstract: Study Objective:To determine the presence and coexistence of viruses and bacterial organisms causing pharyngitis in adults. Design:Open study using diagnostic methods, including rapid anti...

Incidence and Prevalence of Epilepsy in Adults in Eastern Finland

Abstract: In Finland, only limited data exist on the epidemiology of epilepsy in adults. This prompted us to study the incidence and prevalence of epilepsy in a population over 15 years of age, residing in Eastern Finland. In a retrospective study, various medical data sources were used to identify and reexamine all patients with established or suspected epileptic seizures during 1960-1979. A total of 1,233 patients with active epilepsy were identified. Mean annual incidence of epilepsy was 24/100,000. Age-specific incidence ratios tended to increase with advancing age. Prevalence of active epilepsy was 629/100,000. Both prevalence and incidence were higher in males than in females. Age-specific prevalence of active epilepsy increased until 40-50 years of age, and declined in the oldest age groups. Of the various seizure types, highest prevalence ratios were observed for partial secondarily generalized seizures, complex partial seizures, and tonic-clonic seizures. Prevalence of partial seizures and generalized seizures had a different age-related pattern.

The prognostic significance of nuclear DNA content in invasive breast cancer--a study with long-term follow-up.

Abstract: The nuclear DNA content of 351 breast carcinomas was determined by flow cytometry from paraffin-embedded tissue to assess the prognostic significance of DNA ploidy, the DNA index (DI) and the S-phase fraction (SPF). The minimum follow-up of the patients was 22 years, and they were all from a defined urban population. DNA ploidy correlated with histological type and grade, mitotic count and nuclear pleomorphism (P less than 0.0001), and also with axillary nodal status (P = 0.0005), tumour necrosis (P = 0.001), primary tumour size (P = 0.03), menopausal status (P = 0.004) and the presence of distant metastases at the time of the diagnosis (P = 0.04). Survival corrected for intercurrent deaths of the patients with a diploid tumour was better than that of the patients with a non-diploid tumour (P = 0.0001, 48% vs 28% at 25 years). SPF had prognostic significance in both axillary node positive and negative patients, but ploidy and DI only in the node negative group, and their significance was greater in post-menopausal than in premenopausal patients. Axillary nodal status, primary tumour size, histological grade and the type of tumour margin circumscription were the most important independent prognostic factors in Cox's multivariate analysis, and SPF had independent prognostic value, whereas ploidy and DI did not. It is concluded that DNA ploidy, DI and SPF have long-term prognostic significance in breast cancer.

Reading long words embedded in sentences: informativeness of word halves affects eye movements.

Abstract: The possibility was explored that the informativeness of a specific region within a word can influence eye movements during reading. In Experiment 1, words containing identifying information either toward the beginning or toward the end were displayed asymmetrically around the point of fixation so that the reader was initially presented with either the informative or noninformative zone. Words were read with shorter summed initial fixation time when the reading was started from the informative zone. In Experiments 2 and 3, the target words were presented in sentences that were to be comprehended. More attention was given to the informative endings of words than to redundant endings. The latter were also skipped more often. The duration of the first fixation was not affected by information distribution within the word, whereas the second fixation duration was. The results of these experiments lend good support to the hypothesis of immediate lexical control over fixation behavior and to the notion of a convenient viewing position. Three experiments deal with two related issues in the investigation of eye guidance during reading. First, does the information distribution within a word influence fixation time on that word? Second, are fixation locations affected by the information distribution within words? These questions were investigated by observing the eye fixations of readers who were presented with words containing uneven distributions of information. The analyses are based on fixations in two different locations: those coinciding with the informative part of a target word and those coinciding with the uninformative part. There is evidence that the information value of a word may affect the pattern of eye movements during reading. It has been demonstrated that syntactic constraints can affect fixation patterns. Carpenter and Just (1983) and O'Regan (1979) reported that subjects fixated three-letter function words less frequently than content words of equal length. An effect of semantic constraint was observed by Ehrlich and Rayner (1981). Specific words in predictable contexts were fixated less often than the same words in neutral contexts, and when

Volume Corrected Mitotic Index (M/V-INDEX): The Standard of Mitotic Activity in Neoplasms

Abstract: Estimation of mitotic activity by counting the number of mitotic figures per high power fields is subject to many sources of error The microscope fields vary in size in different microscopes, which makes comparisons arbitrary Also the areas covered by neoplastic and non-neoplastic tissue in the microscope image vary in different tumors We found that each microscope could easily be characterized in terms of the size of the microscope field at 40x objective magnification (usually at ocular magnification of 10x) We also found that the number of mitotic figures can be related to the area covered by neoplastic tissue in the microscope field The resulting index, the volume corrected mitotic index (M/V-index) will express the mitotic activity as the number of mitotic figures per square millimeter of neoplastic tissue in the microscope fields The M/V-index will not be subject to the variation in volume fractions of neoplastic tissue between different neoplasms With the M/V-index the mitotic activity as measured in different microscopes can be compared reliably The value of the method is demonstrated in a series of ovarian tumors

The determination of the past and the future of a physical system in quantum mechanics

Abstract: The determination of the past and the future of a physical system are complementary aims of measurements An optimal determination of the past of a system can be achieved by an informationally complete set of physical quantities Such a set is always strongly noncommutative An optimal determination of the future of a physical system can be obtained by a Boolean complete set of quantities The two aims can be reconciled to a reasonable degree with using unsharp measurements

Interleukin-1 alpha stimulation of spermatogonial proliferation in vivo.

Abstract: Interleukin-1 (IL-1) is a family of hormone-like polypeptides originally isolated from cultures of activated monocyte/macrophages and known to act as a potent mediator of inflammation (Dinarello 1984). The effects of IL-1 include augmentation of T and B lymphocyte proliferation (Oppenheim and Gery 1982), but also mitogenic effects on a wide variety of other cells such as fibroblasts (Libby et al. 1985), glial cells (Giulian and Lachman 1985), keratinocytes (Ristow 1987) and chondrocytes (Soder and Madsen 1988). Recent observations indicate that an IL-1-like factor with molecular characteristics similar to the macrophage-derived IL-1 alpha (March et al. 1985) is constitutively produced by the seminiferous tubules (Khan et al. 1987). The present data show that recombinant IL-1 alpha (rIL-1 alpha) stimulates DNA synthesis in intermediate and type B spermatogonia in vivo and suggest that IL-1 alpha may act as a growth factor for spermatogonia.

Hierarchical selection in modular organisms.

Abstract: Modular organisms, such as colonial marine invertebrates and most seed plants, develop by a repetition of physically interrelated subunits colloquially called modules. Modules may include some or all features of single organisms. Modular organisms have no separate germ line; instead, several cell lineages can remain totipotent throughout the life span of the organism or the clone. Due to this somatic embryogenesis, the basic reproductive units are found at the level of the module. The products of modular repetition, i.e. physically coherent organisms, colonies and clones consisting of modules, mainly function as interactive units that modify survival and reproduction at the level of the module. Together these levels of interaction and reproduction make up a hierarchical causal system, which we frequently tend to encapsulate into a single functional unit of selection.

In situ localization of collagen production by chondrocytes and osteoblasts in fracture callus.

Abstract: An experimental model of fracture-healing was used to study the production of types-I and II collagen by in situ hybridization. The distribution of cartilage matrix in callus was determined by histochemical staining. Messenger RNA (mRNA) for cartilage-specific type-II collagen was detectable as early as the fifth day in a small number of cells that had acquired a chondrocyte phenotype but that also contained type-I collagen mRNA, suggesting an ongoing change in the expression of collagen genes. The location of the first chondrocytes, which were adjacent to cortical bone, suggested that they originated from cells that had derived from the periosteum by differentiation. On the seventh day of callus formation, the presence of both type-I and type-II collagen mRNA in chondrocytes of expanding cartilage suggested that most growth occurred by differentiation of mesenchymal cells and less by proliferation of differentiated chondrocytes. Expansion continued until the tenth to fourteenth day, after which the cartilage was replaced by woven bone. This was characterized by the presence of osteoblasts that were active in the synthesis of type-I collagen.

Genetic and environmental factors in sciatica. Evidence from a nationwide panel of 9365 adult twin pairs.

Abstract: The relative roles of genetic and environmental factors in sciatica were studied in the nationwide Finnish twin panel consisting of 9365 adult pairs of the same gender. Morbidity was analysed from two sources of data: the life-long cumulative incidence was measured by a postal questionnaire, and the rate of hospital admission during a 14-year period was measured by record-linkage of the twin panel and the nationwide hospital registry. Altogether 2220 individuals reported sciatica diagnosed by a doctor and 304 were admitted to hospital with a diagnosis of sciatica. The proportion of concordant pairs (calculated from affected pairs) was 17.7% for monozygotic and 12.0% for dizygotic pairs in the life-long cumulative incidence of reported sciatica, and correspondingly 4.6% and 1.9% for those admitted to hospital (a 14-year period) because of sciatica. The estimated heritability was 20.8% for those with reported sciatica and 10.6% for those admitted to hospital. The results show that environmental factors account for more than 80% of the etiology of sciatica, and more than 90% in the case of patients admitted to the hospital. Genetic factors, however, were relatively more significant in individuals under 40.