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Biomedical subjects

M Johansson

Publications and source records attributed to M Johansson.

341 records · Page 19Linked to original sources
PubMedDate not supplied

Characterisation of inter- and intra-molecular interactions of the dengue virus RNA dependent RNA polymerase as potential drug targets.

Our research is directed towards enhancing the understanding of the molecular biology of dengue virus replication with the ultimate goal being to develop novel antiviral strategies based on preventing critical inter- or intra-molecular interactions required for the normal virus life cycle. The viral RNA-dependent RNA polymerase (NS5) and the viral helicase (NS3) interaction offers a possible target for inhibitors to bind and prevent replication. In this study the yeast-two hybrid system was used to show that a small region of NS5 interacts with NS3, and also with the cellular nuclear transport receptor importin-beta. Furthermore, intramolecular interaction between the two putative domains of NS5 can also be detected by the yeast two-hybrid assay. We have also modified the colony lift assay for the beta-galactosidase reporter activity in intact yeast cells which reflects the strength of interaction between two proteins to a microtiter plate format. This assay offers a unique opportunity to screen for small molecule compounds that block physiologically important interactions.

Amino Acid Sequence↗
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Phosphorylation of nucleosides and nucleoside analogs by mammalian nucleoside monophosphate kinases.

Nucleoside monophosphate kinases catalyze the reversible phosphotransferase reaction between nucleoside triphosphates and monophosphates, i.e., monophosphates are converted to their corresponding diphosphate form. These enzymes play an important role in the synthesis of nucleotides that are required for a variety of cellular metabolic processes, as well as for RNA and DNA synthesis. Human tissues contain a thymidylate kinase, a uridylate-cytidylate kinase, five isozymes of adenylate kinase, and several guanylate kinases. Nucleoside monophosphate kinases are also required for the pharmacological activation of therapeutic nucleoside and nucleotide analogs. This overview is focused on the substrate specificity, tissue distribution, and subcellular location of the mammalian monophosphate kinases and their role in the activation of nucleoside and nucleotide analogs.

Animals↗
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Expression of the proteolytic factors, tPA and uPA, PAI-1 and VEGF during malignant glioma progression.

Various proteases and their inhibitors have been shown to be important in tumor invasion. Angiogenesis is further a prerequisite for the growth and progression of solid tumors. Since these systems are functionally linked, in situ hybridization and in situ zymography were used to investigate the spatial and temporal expression of factors representative of the plasmin/plasminogen system and of an angiogenic factor in the BT4C glioma model. This tumor is invasive with a high grade of neovascularization. Tissue-type plasminogen activator urokinase-type plasminogen activator and plasminogen activator inhibitor-1 mRNA were expressed in glioma cells during the entire tumor growth. Early in the tumor development the expression was found throughout the small tumor (approximately 10 mm3) while later in the time course the expression was found predominantly in the invasive tumor border of the tumor. The in situ zymography demonstrated that the plasminogen activators were translated into functional proteins. Vascular endothelial growth factor mRNA was expressed following a similar spatial and temporal pattern with an early expression in the entire small tumor while later, in larger tumors, it was exclusively expressed in the invasive tumor edge. In normal brain, the ventricular ependyma, meninges, as well as scattered neurons expressed tissue-type plasminogen activator mRNA. Vascular endothelial growth factor mRNA was observed in the choroid plexus, and in scattered cells in normal brain tissue. Our finding may suggest a functional co-operation of tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor-1 and vascular endothelial growth factor during glioma progression. This model could be of value when evaluating different treatment modalities aimed at blocking the migrating capacity and growth of glial tumors.

Animals↗
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Urine leaks in renal transplant patients. Diagnostic usefulness of sonography and renography.

We evaluated the utility of sonography and nuclear medicine renography in the detection of urine leaks in 57 renal transplant patients. Sonography and renography were equally sensitive in detecting leaks. But renography was more specific and therefore accurate (p < 0.0001) in detecting leaks. Urine leaks should be considered on sonography, which is often the first imaging study ordered in evaluating renal transplants, with new or increasing peritransplant fluid collections. Leaks should be confirmed by renography before performing additional invasive radiologic or surgical procedures.

Adolescent↗
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Climate and environment change in patients with chronic airway obstruction.

Psychological, clinical, and pulmonary physiological measurements were studied in ten patients with weather-sensitive chronic airway obstruction during one month in Gothenburg, Sweden, and immediately after for one month in the Canary Islands, a change to a drier and warmer climate. All patients improved according to psychological tests and claimed to be better. Objective measurements including peak expiratory flow rate, airway conductance, static lung volumes, and elastic lung recoil showed improvement in eight of ten patients, a change that we believe is due to the effect of climate.

Adult↗
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Cloning and characterization of highly polymorphic porcine microsatellites.

A size-fractionated (200-400 bp) porcine genomic library was screened with the dinucleotide motifs (TG)n and (TC)n. The number of TG- and TC-positive clones was 83 and four, respectively, implying that the former motif is more frequent in the porcine genome, as previously reported in other species. Twenty-six TG-clones were sequenced, and the number of repeats varied between 16 and 42 with different compositions of the repetitive sequences; 17 clones had a perfect stretch of TG-repeats, four had imperfect stretches, and five had a compound structure with TG-repeats followed by TC-repeats. Primers for DNA amplification using the polymerase chain reaction (PCR) were synthesized for six loci. Ten unrelated individuals (two wild boars and eight domestic pigs of the Swedish Yorkshire breed) were screened for microsatellite polymorphism. All six microsatellite loci were polymorphic with two to seven alleles and observed heterozygosities in the range of 0.42-0.84; the inheritance of the observed polymorphism was confirmed by family studies. The characteristics of microsatellites make them highly suitable as genetic markers, and these microsatellites were isolated as a part of a pig gene mapping project.

Animals↗
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Genetic analysis of the gene for porcine submaxillary gland mucin: physical assignment of the MUC and interferon gamma genes to chromosome 5.

Genetic variation at the porcine submaxillary gland mucin (MUC) locus was revealed by RFLP analysis. A three-allele system was defined, and codominant inheritance was confirmed using a three-generation pedigree comprising 10 founder individuals, 26 F1 animals, and 200 F2 offspring. Linkage analysis was performed against a set of 56 genetic markers. The mucin locus was assigned to a previously reported linkage group comprising the markers interferon gamma (IFNG), diacylglycerol kinase (DAGK), and an anonymous microsatellite (S0092). Furthermore, the genes for mucin and interferon gamma were physically localized to porcine chromosome 5q2.3 and 5p1.2-q1.1 by fluorescence and radioactive in situ hybridization, respectively, thereby assigning four new markers to chromosome 5. This chromosome shares homologies with chromosome 5 in cattle and chromosome 12 in humans.

Animals↗
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Imaging of nicotinic and muscarinic receptors in Alzheimer's disease: effect of tacrine treatment.

Functional imaging techniques offer new possibilities for further understanding of changes in functional correlates of structural and biological changes in dementia disorders like Alzheimer's disease (AD). Regional disturbances in glucose metabolism and cerebral blood flow are known to occur in AD brains and probably roughly correlate to changes in neurotransmitter activities. A proper estimate would be to visualize the neuroreceptors themselves. In this study the cholinergic nicotinic and muscarinic receptors were studied in brain by positron emission tomography (PET). The rate constant k2* (s) (-)11C-nicotine was significantly higher (+43%) in temporal cortex of AD patients compared to controls (p < 0.017) indicating a lower binding of 11C-nicotine in AD brains compared to controls. Treatment with the cholinesterase inhibitor tacrine (80 mg daily) during 3 months to AD patients resulted in a mean plasma concentration of 7.7 +/- 0.8 ng/ml and a corresponding inhibition of the cholinesterase activity in plasma by 34 +/- 5%. A significantly lower k2* (increased binding) for 11C-nicotine binding (-15%; p < 0.006) was obtained in the temporal cortex after 3 months of treatment compared to prior treatment. The muscarinic antagonist 11C-benztropine was used to visualize muscarinic receptors and the binding capacity of 11C-benztropine (KR) was found to be decreased in the temporal cortex after 3 months of tacrine treatment.

Aged↗
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Steady-state pharmacokinetics of tacrine in long-term treatment of Alzheimer patients.

The pharmacokinetics of the cholinesterase inhibitor tacrine was studied in 5 Alzheimer patients during 12-31 months of treatment. A mean average steady-state concentration in plasma ranging from 1.1 to 30 ng/ml was obtained with doses ranging from 40 to 160 mg of tacrine daily. During treatment with 80 mg daily a maximal plasma concentration of tacrine (8.7 +/- 0.6 ng/ml) was obtained 1.3 +/- 0.2 h after intake of the morning dose. The mean elimination half-life was estimated at 5-7 h and remained unchanged when the tacrine dose was increased. The plasma concentration of tacrine was stable during long-term treatment with tacrine and no tolerance was observed regarding its cholinesterase inhibitory effect. A maximal 40% inhibition of plasma cholinesterase (ChE) activity and 60% inhibition of acetylcholinesterase activity in red blood cells was measured following treatment with the highest dose of 160 mg tacrine daily. A significant correlation was obtained between the plasma concentration of tacrine and the inhibition of ChE activity (p < 0.001). The tacrine concentration in CSF was measured in each patient on 1-3 occasions during the treatment and the ratio CSF/plasma concentration was estimated to be 0.47 +/- 0.09 (n = 11).

Acetylcholinesterase↗
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Magic Lite Chlamydia immunoassay in urogenital samples and urine versus chlamydial culture.

Magic Lite Chlamydia assay (commercial test kit for the identification of Chlamydia trachomatis) was evaluated on urogenital samples and urine with chlamydial culture as the reference method. The sediment of the transportation buffer of specimens which were Magic Lite positive but culture negative or toxic was investigated for elementary bodies with fluorescein-labelled anti-chlamydial antibodies. The prevalence of chlamydial infection among the 577 men investigated was 13.7% as estimated by culture and direct immunofluorescence and 6.4% among the 173 women. In order to improve the sensitivity a cut-off value below that recommended by the manufacturer was used. The sensitivity of Magic Lite in male urethral specimens was then 60.8% and that in female urethral/cervical specimens 90.9%. The specificity was 99.6% and 100%, respectively. In urine specimens the sensitivity of Magic Lite was 63.3% (men) and 63.6% (women). The specificity was 99.4% and 100%, respectively. The sensitivity of Magic Lite on male urethral specimens was related to the number of inclusion bodies per well in culture and it was higher among men attending with clinical findings of urethritis (69%) than among asymptomatic men sampled as a screening procedure (36%) (P < 0.05). Corresponding differences between the sexes and between those with and without symptoms were not noted for Magic Lite applied on urine samples.

Adolescent↗
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Five new bioactive sesquiterpenes from the fungus Radulomyces confluens (Fr.) Christ.

The three protoilludanes radulone A (1), radulone B (2) and radudiol (3), the illudalane radulactone (4) and the illudane radulol (5) were isolated from the extracts of the culture fluids of the basidiomycete Radulomyces confluens. The structures of the five new compounds were determined by spectroscopic techniques. Radulone A (1) is a potent inhibitor of human and bovine platelet aggregation stimulated by different agonists, inhibiting preferentially the aggregation of human platelets induced by ADP with an IC50 value of 2 microM. In addition 1 exhibits cytotoxic and antimicrobial activities. The other four compounds exhibited weak antimicrobial and cytotoxic activity.

Animals↗
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Coprinol, a new antibiotic cuparane from a Coprinus species.

Coprinol, a new antibacterial cuparane, was isolated from fermentations of a Coprinus sp. Its biological activities were investigated and its structure was elucidated by spectroscopic methods. The new antibiotic exhibited activitiy against multidrug-resistant Gram-positive bacteria in vitro. Two derivatives were synthesized and their activities compared to the parent compound.

Adenocarcinoma↗
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Quality functions for requirements engineering in system development methods.

Based on a grounded theory framework, this paper analyses the quality characteristics for methods to be used for requirements engineering in the development of medical decision support systems (MDSS). The results from a Quality Function Deployment (QFD) used to rank functions connected to user value and a focus group study were presented to a validation focus group. The focus group studies take advantage of a group process to collect data for further analyses. The results describe factors considered by the participants as important in the development of methods for requirements engineering in health care. Based on the findings, the content which, according to the user a MDSS method should support is established.

Decision Making, Computer-Assisted↗
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Reference data for evaluation of occupationally noise-induced hearing loss.

Relevant reference data are required in order to determine the effect from occupational noise exposure on hearing. Pure-tone averages (PTA) of hearing threshold levels simplify the evaluation for audiometric frequencies typically affected by noise. The present study provides reference data of high frequency (HF) PTA over 3, 4 and 6 kHz for a general adult population, aged from 20 to 79 years, not exposed to hazardous occupational noise. The results are presented as statistical distributions of HF PTA values as functions of age, and as prevalence of different degree of HF PTA in the age groups 20-29, 30-39, 40-49, 50-59, 60-69 and 70-79 years.

Adult↗
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Effect of estradiol on tumor growth, cell kinetics and p53 oncoprotein expression in human endometrial adenocarcinoma heterotransplanted into nude mice.

To study the importance of estradiol concentrations in which tumors are growing to progression of tumor growth and cell kinetics, we have used a human tumor-nude mice model. In this model a human endometrial adenocarcinoma with estradiol independent but estradiol-responsive growth phenotype (i.e. the tumor was capable of growing in absence of estradiol but its growth could be stimulated by estradiol at the start of preparation phase) was examined. In the preparation phase pieces from this tumor were transplanted into nude mice, randomly divided into two groups, one with and one without estradiol treatment. After 18 months growth in these different hormone conditions the tumors were measured for p53 protein expression and pieces from both these groups were again transplanted into oophorectomized nude mice, each group being randomly allocated to two subgroups, one with and one without estradiol treatment (experimental phase). Tumor growth was measured during the experimental phase, whereas cell kinetic parameters and steroid receptor concentrations were analyzed after the experimental phase. Our findings indicate that progression of the growth phenotype is independent of estradiol conditions in which human endometrial adenocarcinomas are grown. Long-term growth in estradiol-poor conditions results in estradiol resistance of the cell cycle, probably accompanied by overexpression of the p53 protein. Tumor growth in estradiol-rich conditions, however, may protect, at least to some extent, the same tumor, which retains higher sensitivity of cell proliferation to estradiol and normal production of the p53 protein despite progressive changes in growth regulation.

Animals↗
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Growth interaction between different tumor populations in human endometrial adenocarcinoma growing in nude mice.

In these studies of tumor cell growth interaction we have used two tumors differing from each other in sensitivity to estradiol, transplanted to opposite sites of the same nude mice. In the first experiment we found that the growth of an estradiol-sensitive tumor may be delayed by the presence of an estradiol-resistant tumor in the same animal. Although the growth pattern was changed, proliferative activity, as reflected in the S-phase fraction measured by flow cytometry, and the steroid receptor concentrations were unchanged. Increase of circulating estradiol, however, protects the estradiol-sensitive population from this down-regulation of growth. Findings in a second experiment suggest that this growth delay is probably caused by changes such as decrease in labelling index, increase of non BrdU-incorporating cells in the S-phase, and cell loss in estradiol-sensitive tumors. We concluded that the estradiol-resistant tumor population may secrete some factor(s) acting as endocrine product(s) which may delay the growth of estradiol-sensitive cell populations when the tumors are grown in an estradiol-poor environment. If our model also represents interactions between tumor subpopulations within a single tumor, these findings may have implications for our understanding of the biology of tumor progression in some hormone-related human tumors.

Adenocarcinoma↗