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Biomedical subjects

M Johansson

Publications and source records attributed to M Johansson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Changes in intervention and outcome in elderly patients with subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The elderly constitute a significant and increasing proportion of the population. The aim of this investigation was to study time trends in clinical management and outcome in elderly patients with subarachnoid hemorrhage. METHODS: Two hundred eighty-one patients >/=65 years of age with aneurysmal subarachnoid hemorrhage who were accepted for treatment at the Uppsala University Hospital neurosurgery clinic during 1981 to 1998 were included. Hunt and Hess grades on admission, specific management components, and clinical outcomes were recorded. Three periods were compared: A, 1981 to 1986 (before neurointensive care); B, 1987 to 1992; and C, 1993 to 1998. RESULTS: The volume of elderly patients (>/=65 years of age) increased with time, especially patients >/=70 years of age. Furthermore the proportion of patients with more severe clinical conditions increased. A greater proportion of patients had a favorable outcome (A, 45%; B, 61%; C, 58%) despite older ages and more severe neurological and clinical conditions. In period C, Hunt and Hess I to II patients had a favorable outcome in 85% of cases compared with 64% in period A. This was achieved without any increase in the number of severely disabled patients. CONCLUSIONS: Elderly patients with subarachnoid hemorrhage can be treated successfully, and results are still improving. The introduction of neurointensive care may have contributed to the improved outcome without increasing the proportion of severely disabled patients. A defeatist attitude toward elderly patients with this otherwise devastating disease is not justified.

Age Distribution↗
PubMed2001

Nucleoside analog cytotoxicity and bystander cell killing of cancer cells expressing Drosophila melanogaster deoxyribonucleoside kinase in the nucleus or cytosol.

We have recently shown that the overexpression of Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (Dm-dNK) in cancer cell lines increases the cells' sensitivity to several cytotoxic nucleoside analogs and the enzyme may accordingly be used as a suicide gene in combined gene/chemotherapy treatment of cancer. To further characterize the enzyme for possible use as a suicide gene, we constructed a replication-deficient retroviral vector that expressed either the wild-type enzyme that localizes to the cell nucleus or a mutant (arg247ser) that localizes to the cytosol. A thymidine kinase-deficient osteosarcoma cell line was transduced with the recombinant virus and we compared the sensitivity and bystander cell killing when the cell lines were incubated with the pyrimidine nucleoside analogs (E)-5-(2-bromovinyl)-2'-deoxyuridine and 1-beta-D-arabinofuranosylthymine. In summary, we showed that the cells' sensitivity and the efficiency of bystander cell killing were not dependent on whether Dm-dNK was located in the nucleus or cytosol.

Amino Acid Sequence↗
PubMed2001

Bystander effects of nucleoside analogs phosphorylated in the cytosol or mitochondria.

The efficiency of nucleoside kinase suicide gene therapy for cancer is highly dependent on "bystander" cell killing, i.e., the transfer of cytotoxic phosphorylated nucleoside analogs to cells adjacent to those expressing the suicide enzyme. We have recently studied the possible use of mitochondrial nucleoside kinases as suicide genes. In the present study, we investigated if nucleoside analogs phosphorylated in the mitochondrial matrix cause bystander killing. We used deoxycytidine kinase-deficient Chinese hamster ovary cells reconstituted with deoxycytidine kinase targeted to either the cytosol or mitochondria matrix and determined the bystander cell killing when these cells were incubated with the nucleoside analogs 1-beta-D-arabinofuranosylcytosine and 2',2'-difluorodeoxycytidine. A bystander effect occurred when nucleoside analogs were phosphorylated in the cytosol, but not when these compounds were phosphorylated in the mitochondria. These findings suggest that nucleoside kinases targeted to the mitochondrial matrix have limited use in suicide gene therapy when efficient bystander cell killing is required.

Animals↗
PubMed2001

[A controlled trial with prolonged follow up: percutaneous intervention in acute myocardial infarction is equivalent to thrombolytic therapy].

Previous studies comparing percutaneous coronary intervention (PCI) with thrombolysis for treatment of myocardial infarction with ST-elevation have in meta-analyses but not in randomized trials shown that PCI is more effective. Despite a large volume of primary PCI performed in Sweden no controlled trials have been carried out. The present study included 96 patients with myocardial infarction with ST-segment elevation treated with primary PCI 1995-1998. The main indications were shock (15 cases), contraindication to thrombolysis (24 cases), as an alternative to thrombolysis (57 cases), with a mortality in the respective groups of 67, 25 and 10 percent. Controls matched for age and infarct location and treated with thrombolysis could be identified for 55 of the patients treated with PCI. After four years 40 percent and 52 percent of the patients treated with PCI and thrombolysis respectively reached the combined endpoint of death/myocardial infarction/revascularization/angina pectoris (not significant). In conclusion, the study shows that primary PCI in patients with myocardial infarction with ST-segment elevation can be performed safely also in Sweden.

Aged↗
PubMed2001

Three molecules of ubiquinone bind specifically to mitochondrial cytochrome bc1 complex.

Bifurcated electron flow to high potential "Rieske" iron-sulfur cluster and low potential heme b(L) is crucial for respiratory energy conservation by the cytochrome bc(1) complex. The chemistry of ubiquinol oxidation has to ensure the thermodynamically unfavorable electron transfer to heme b(L). To resolve a central controversy about the number of ubiquinol molecules involved in this reaction, we used high resolution magic-angle-spinning nuclear magnetic resonance experiments to show that two out of three n-decyl-ubiquinones bind at the ubiquinol oxidation center of the complex. This substantiates a proposed mechanism in which a charge transfer between a ubiquinol/ubiquinone pair explains the bifurcation of electron flow.

Animals↗
PubMed2001

Dual mechanisms of 9-beta-D-arabinofuranosylguanine resistance in CEM T-lymphoblast leukemia cells.

The guanine nucleoside analog araG is selectively toxic to T-lymphoblasts and has recently shown promise in treatment of lymphoid malignancies of T-cell origin. The molecular mechanism of this tissue-selective cytotoxicity is, however, yet unclear. AraG is phosphorylated, and thereby pharmacologically activated, by the mitochondrial deoxguanosine kinase and the cytosolic/nuclear deoxycytidine kinase. We have recently shown that araG is predominantly incorporated into mitochondrial DNA of cancer cell lines, which suggests a role of mitochondria as its pharmacological target. In the present study, we have generated araG-resistant CEM T-lymphoblast cell lines and show that araG resistance may occur by two separate molecular mechanisms that can occur sequentially. The first mechanism is associated with a decrease of araG incorporation into mitochondrial DNA, and the second event is associated with loss of dCK activity.

Antineoplastic Agents↗
PubMed2001

Cloning and expression of a novel human glutaredoxin (Grx2) with mitochondrial and nuclear isoforms.

Glutaredoxin (Grx) is a glutathione-dependent hydrogen donor for ribonucleotide reductase. Today glutaredoxins are known as a multifunctional family of GSH-disulfide-oxidoreductases belonging to the thioredoxin fold superfamily. In contrast to Escherichia coli and yeast, a single human glutaredoxin is known. We have identified and cloned a novel 18-kDa human dithiol glutaredoxin, named glutaredoxin-2 (Grx2), which is 34% identical to the previously known cytosolic 12-kDa human Grx1. The human Grx2 sequence contains three characteristic regions of the glutaredoxin family: the dithiol/disulfide active site, CSYC, the GSH binding site, and a hydrophobic surface area. The human Grx2 gene, located at chromosome 1q31.2--31.3, consisted of five exons that were transcribed to a 0.9-kilobase human Grx2 mRNA ubiquitously expressed in several tissues. Two alternatively spliced Grx2 mRNA isoforms that differed in their 5' region were identified. These corresponded to alternative proteins with a common 125-residue C-terminal Grx domain but with different N-terminal extensions of 39 and 40 residues, respectively. The 125-residue Grx domain and the two full-length variants were expressed in E. coli and exhibited GSH-dependent hydroxyethyl disulfide and dehydroascorbate reducing activities. Western blot analysis of subcellular fractions from Jurkat cells with a specific anti-Grx2 antibody showed that human Grx2 was predominantly located in the nucleus but also present in the mitochondria. We further showed that one of the mRNA isoforms corresponding to Grx2a encoded a functional N-terminal mitochondrial translocation signal.

Amino Acid Sequence↗
PubMed2001

Decay of discrete nonlinear Schrödinger breathers through inelastic multiphonon scattering.

We consider the long-time evolution of weakly perturbed discrete nonlinear Schrödinger breathers. While breather growth can occur through nonlinear interaction with one single initial linear mode, breather decay is found to require excitation of at least two independent modes. All growth and decay processes of lowest order are found to disappear for breathers larger than a threshold value.

Journal Article↗
PubMed2001

Comparison of nitrate tolerance between different populations of the common frog, Rana temporaria.

Euthrophication-associated changes in the physical and biological environment of lakes and ponds are potentially a source of major stress for many aquatic organisms. In Scandinavia, the nitrate concentrations in lakes and ponds decrease towards north due to a naturally lower productivity of the habitats, but also due to lower supplementation of anthropogenic nitrogen. A chronic experiment using ecologically relevant concentrations of sodium nitrate (0-5000 micro gl(-1)) was used to test whether common frog (Rana temporaria L.) larvae from northern parts of Scandinavia are less well adapted to cope with high nitrate concentrations than those from the southern parts. Slight, but significant differences in nitrate tolerance, as measured in terms of growth rate and size at metamorphosis, between the two regions were found. High concentrations of nitrate reduced the growth rates and metamorphic size in north, but not in south. However, there was no clear-cut impact of high nitrate concentrations on developmental rate or on mortality until metamorphosis. The general lack of large effects of nitrate treatment on the response variables suggests that nitrates per se do not pose any significant threat to the development of R. temporaria tadpoles under a natural range of concentrations. This was confirmed in an acute test where results suggest that ammonia and nitrite, compounds seldom found in high concentrations in Fennoscandian lakes, are possibly responsible for the larger negative effects of "nitrate" observed in previous studies of amphibians.

Animals↗
PubMed2001

Autistic spectrum disorders in Möbius sequence: a comprehensive study of 25 individuals.

The prevalence of autistic disorder was analysed in 25 individuals with Möbius sequence, a disorder with brain-stem dysfunction. The sample consisted of 18 males and seven females (20 participants were aged 2 to 22 years, and five were aged 1, 19 and 23 months, and 55 years old). Participants were recruited after a nationwide call and were part of a multidisciplinary study of individuals with Möbius sequence. They were given a meticulous neuropsychiatric examination including standardized autism diagnostic interviews. Ten individuals had an autistic spectrum disorder. Six of these met all diagnostic criteria for autism. In 23 individuals cognitive development could be assessed. Eight of those 23 patients had clear learning disability and six individuals were functioning in the normal but subaverage range. Autistic spectrum disorder and learning disability occurred in more than a third of the examined patients. Considering the hospital-based nature of the sample, these findings may be overestimates. Nevertheless, awareness of this coexistence is important in the diagnosis and habilitation care of children with Möbius sequence. Moreover, the results provide further support for the notion of a subgroup of autistic spectrum disorders being caused by first trimester brain-stem damage.

Adolescent↗
PubMed2001

Wild birds as a possible natural reservoir of Borna disease virus.

The natural reservoir of Borna disease virus (BDV) is unknown. In this paper, we show that mallards (Anas platyrhyncos) and jackdaws (Corvus monedula) can be subclinically infected carriers of this virus. From faecal samples collected at a bird pond, we were able to amplify fragments of the BDV p24 and p40 genes. Following cloning and sequencing, a phylogenetic analysis revealed that these birds carry strains of BDV closely related to but distinct from the reference strains BDV V and He/80. To our knowledge, this is the first confirmed finding of BDV in wild birds.

Animals↗
PubMed2001

Additive IOP-reducing effect of latanoprost in patients insufficiently controlled on timolol.

PURPOSE: To evaluate the effect on intraocular pressure (IOP) of switching from timolol to latanoprost or adding latanoprost to timolol in patients with open angle glaucoma or ocular hypertension where IOP is not adequately controlled with timolol. METHODS: This was a 6-week, double-masked, randomised multi-centre study. 53 patients with primary open angle glaucoma, capsular glaucoma, or ocular hypertension with an IOP of at least 21 mmHg on current therapy were recruited. After a run-in period of at least 2 weeks on timolol, 5 mg/ml twice daily, patients were randomised to one of three groups. One group continued on timolol, one switched from timolol to latanoprost, 50 microg/ml once daily, and a third group received latanoprost in addition to timolol. The efficacy was evaluated by comparing IOP at 9 AM at baseline and after 6 weeks of treatment. RESULTS: IOP at baseline and after 6 weeks of treatment (mean +/- SEM) were 24.2 +/- 0.9 and 23.8 +/- 1.0 mmHg (n = 16) for patients continuing on timolol, 26.3 +/- 1.2 and 19.6 +/- 1.1 mmHg (n = 17) for patients switching to latanoprost, and 23.2 +/- 1.0 and 17.5 +/- 0.8 mmHg (n = 17) for patients with combined treatment. Adding latanoprost to timolol reduced IOP with 5.9 +/- 0.9 mmHg (p < 0.001) and switching from timolol to latanoprost reduced IOP with 5.0 +/- 0.9 mmHg (p < 0.001), which caused in each group a significant IOP reduction of about 25%. CONCLUSIONS: The effect of latanoprost was additive to that of timolol, and a good effect on IOP reduction was also achieved by switching from timolol to latanoprost, suggesting that a switch in many patients is an effective alternative to combination treatment.

Adult↗
PubMed2001

Prediction of post-operative glomerular filtration rate after nephrectomy for renal malignancy.

The importance of a correct estimation of contralateral renal function in cases of renal malignancy is obvious, necessitating a conservative approach to tumour resection when function of the contralateral kidney is markedly reduced. The aim of the present study was to determine the accuracy of preoperative gamma camera renography and (51)Cr-EDTA clearance to predict the glomerular filtration rate (GFR) early and up to 6 months after nephrectomy for renal malignancy. Patients (n=40) underwent both gamma camera renography ((99m)TC-DTPA) and (51)Cr-EDTA clearance preoperatively, whereas (51)Cr-EDTA clearance was measured within 1 week and up to 6 months after nephrectomy. The single kidney GFR values of the contralateral kidneys were estimated preoperatively and then compared with the post-operative (51)Cr-EDTA clearance values. The predicted GFR values were lower compared with the measured post-operative (51)Cr-EDTA clearance values (45 +/- 2 vs. 54 +/- 3 ml min(-1) 1 week after nephrectomy and 53 +/- 3 ml min(-1) 6 months later, P<0.01, respectively). The difference between the measured and predicted GFR was larger in patients below the median age of 60 years (P<0.05) and confined to patients with a relative uptake of >30% by the tumour affected kidney. Prediction of post-operative GFR by non-invasive renal function tests performed prior to surgery for renal malignancy underestimate post-operative GFR when the function of the tumour affected kidney is preserved, indicating an adaptive GFR increase in these cases.

Aged↗
PubMed2001

Immunological memory in B-cell-deficient mice conveys long-lasting protection against genital tract infection with Chlamydia trachomatis by rapid recruitment of T cells.

The role of antibodies and antigen deposition for the development of immunological memory has been incompletely investigated. We addressed whether long-term protection and T-cell memory can be stimulated against a genital tract infection with human Chlamydia trachomatis serovar D in B-cell-deficient (muMT) mice. At 6 months following a primary infection with C. trachomatis, both muMT and wild-type (WT) mice exhibited strong and comparable protection against reinfection. Evidence of long-lasting CD4+ T-cell memory was found in both muMT and WT mice, typified by comparable delayed-type hypersensitivity (DTH) reactions against chlamydial antigens. No bacterial or chlamydial DNA was found in the genital tract of muMT memory mice, suggesting that immunological memory was maintained in the absence of antigen. Whereas few T cells were present in the genital tract of memory mice, rapid recruitment of CD4+, and some CD8+, T cells into the genital tract tissue was observed after challenge with live bacteria. Accumulation of T cells in the genital tract was preceded by a short transient infection of similar magnitude in both muMT and WT memory mice, arguing against a long-term protective role of local antibodies. The rapid recruitment of CD4+ T cells into the genital tract was associated with a transient detection of interferon-gamma (IFN-gamma) mRNA in the genital tract in chlamydia-immune memory mice, which was not found in naïve, challenged mice. Thus, long-term protection in the genital tract against C. trachomatis infection is conveyed by IFN-gamma-producing CD4+ memory T cells, which appear to be maintained in the absence of antibodies and local antigen deposition.

Animals↗
PubMed2001

Evaluation of the significance of dietary folate from wild vegetables in Vietnam.

Data on the overall dietary folate intakes among high-risk groups in poor countries is very limited. Vegetables are considered good sources but the evaluation of their contribution is hampered by the lack of data on folate concentrations in many traditional foods. Data on the analysis of folate concentrations in 16 wild vegetables used in the Mekong Delta and the Central Highlands in Vietnam and an evaluation of the relative importance of different foods in folate intakes of women is presented. Vegetable samples were collected in four study villages, blanched and frozen samples were transported to Sweden for analysis. Freeze-dried samples were analysed for total folate quantification using a commercial radio protein binding assay. Daily folate intakes among women were estimated from 7-day food frequency interviews with 213 women. The folate concentration in the vegetable samples ranged from 10 to 96 microg/100 g. The mean estimated daily folate intake among the 213 women in the study areas was 251 microg. Vegetables contributed approximately one-third of the daily folate intake, of which 72% and 42%, respectively, in the two regions was from wild vegetables. A majority of the women (87%) got some dietary folate from wild vegetables and nearly one-third had mean daily folate intakes of > 50 microg from such hidden food sources. The evaluation of dietary folate is complicated by data gaps in food composition tables, the unreliability of existing food data, variations between methods used for folate analysis and limited understanding of the bioavailability of food folate.

Adult↗
PubMed2001

Randomized controlled trial of vestibular rehabilitation combined with cognitive-behavioral therapy for dizziness in older people.

OBJECTIVE: To evaluate the effectiveness of vestibular rehabilitation combined with cognitive behavioral therapy in the treatment of dizziness in older people. STUDY DESIGN AND SETTING: A randomized controlled design was used with patients recruited via an advertisement. Nine patients completed treatment and 10 served as waiting-list controls. The intervention lasted 7 weeks with 5 weekly group sessions and consisted of vestibular exercises. Cognitive behavioral therapy components were added to promote relaxation, reduce anxiety, and avoidance of feared situations and movements. RESULTS: Statistically significant improvements on walking time, 2 dizziness provocative movements, and on the Dizziness Handicap Inventory, but no effects on the Romberg or anxiety and depression. Of the treated patients, 89% reached statistical significant improvement on the total inventory score. CONCLUSION: Cognitive behavioral therapy combined with vestibular rehabilitation decreases dizziness in older people. SIGNIFICANCE: These findings indicate that cognitive behavioral therapy can be combined with vestibular rehabilitation in the treatment of dizziness.

Aged↗