Biomedical subjects

M Johansson

Publications and source records attributed to M Johansson.

At least 37 records · Page 2Linked to original sources

PubMed2004

Clinical outcome after endovascular coil embolization in elderly patients with subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is not an unusual disease in an elderly population. The clinical outcome has improved over time. It has been suggested that elderly SAH patients would benefit from endovascular aneurysm treatment. The aim of this study was to evaluate technical results and clinical outcome in a series of elderly SAH-patients treated with endovascular coil embolization. Sixty-two patients (> or = 65 years) presenting with aneurysmal SAH underwent early endovascular coil embolization at Uppsala University Hospital between September 1996 and December 2000. In all 62 cases included in the study, endovascular coil embolization was considered the first line of treatment. Admission variables, specific information on technical success, degree of occlusion and procedural complications, and outcome figures were recorded. Clinical grade on admission was Hunt and Hess (H&H) I-II in 39%, H&H III in 27% and H&H IV-V in 34% of the patients. The proportion of posterior circulation aneurysms was 24%. Coil embolization was successfully completed in 94%. The degree of occlusion of the treated aneurysm was complete occlusion in 56%, neck remnant in 21%, residual filling in 11%, other remnant in 5% and not treated in 6%. The rate of procedural complications was 11%. Outcome after 6 months was favorable in 41%, severe disability in 36% and poor in 22%. Favorable outcome was achieved in 57% of the H&H I-II patients, 47% of the H&H III patients and 17% of the H&H IV-V patients. Endovascular aneurysm treatment can be performed in elderly patients with SAH with a high level of technical success, acceptable aneurysm occlusion results, an acceptable rate of procedural complications and fair outcome results.

Age Factors↗

PubMed2004

An overview of OSPAR priority compounds and selection of a representative training set.

The aim of our study was to chemically characterize a set of priority substances in order to systematically select a representative set of heterogeneous substances for experimental studies of their persistence, bioaccumulation and toxicity (PBT). By including structurally diverse compounds in a PBT-screening protocol, structure-based knowledge would be achieved as a basis for more detailed studies of specific compounds from certain regions of the chemical domain. Initially compounds on the Draft Preliminary List of Substances of Possible Concern presented by the Oslo & Paris Commission (OSPAR) were subjected to broad chemical characterization using Principal Component Analysis (PCA). Molecular weight and seven physico-chemical descriptors collected from the literature, five calculated properties and 25 constitutional descriptors were used in this characterization. The OSPAR list represents a broad spectrum of substances, and thus provides a good basis for selecting heterogeneous substances. D-optimal design was applied to the first four principal components derived in the PCA. In total, 19 structurally diverse substances were chosen as representatives of the chemical domain including 353 substances.

Hazardous Substances↗

PubMed2004

Non-gastric H+/K+ ATPase is present in the microvillous membrane of the human placental syncytiotrophoblast.

In humans, the non-gastric H(+)/K(+)ATPase (ATP1AL1) has previously been shown to be expressed in the epithelia of skin, kidney and colon. In this study we tested the hypothesis that the non-gastric H(+)/K(+)ATPase is localized to the syncytiotrophoblast, the transporting epithelium of the human placenta. Microvillous (MVM) and basal plasma membranes (BM) of the syncytiotrophoblast were isolated from term placenta and membrane proteins were separated using SDS-PAGE. The ATP1AL1 protein was identified as a 114 kD band in both MVM and BM by Western blot, however, the protein was more abundant in the MVM. Using immunocytochemistry H(+)/K(+)ATPase protein was localized in MVM but not BM. We constructed primers specific for ATP1AL1 and performed RT-PCR on RNA isolated from human placenta and human kidney. A product of the expected size could be detected in both tissues after 30 cycles of amplification. The sequence identity of this 517 nucleotide product was confirmed by sequencing and found to be identical to the human non-gastric H(+)/K(+)ATPase. The activity of this proton pump appears to be low in normal healthy placental at term, however, it is speculated that MVM non-gastric H(+)/K(+)ATPase may be important in pathological states. In conclusion, non-gastric H(+)/K(+)ATPase is present in the microvillous plasma membrane of the transporting epithelia of the human placenta.

Blotting, Western↗

PubMed2004

5-Fluoro-2'-deoxyuridine has effects on mitochondria in CEM T-lymphoblast cells.

Fluoropyrimidines are useful anticancer agents and the compound 5-fluoro-2'-deoxyuridine (FdUrd) plays an important role in chemotherapy of colon cancers. Several nucleoside analogs, such as 3'-azido-2',3'-dideoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC), can be incorporated into and cause depletion of mitochondrial DNA (mtDNA). These drugs are known to cause mitochondrial toxicity after prolonged treatment in patients. In this study we demonstrate that FdUrd reduces the mtDNA content and the expression level of the mtDNA encoded cytochrome c oxidase (COX II) in a CEM T-lymphoblastic cell line.

Antimetabolites, Antineoplastic↗

PubMed2004

Investigation of the substrate recognition of Drosophila melanogaster nucleoside kinase by site directed mutagenesis.

The deoxyribonucleoside kinase of Drosophila melanogaster (Dm-dNK) has a broad substrate specificity and a higher catalytic rate than other known deoxyribonucleoside kinases. Therefore it is a natural candidate for possible use as a suicide gene in combined gene/chemotherapy of cancer. We have performed site directed mutagenesis and tested different truncated forms of the enzyme in order to increase the affinity for ganciclovir.

Animals↗

PubMed2004

Reduced sympathetic responsiveness as well as plasma and tissue noradrenaline concentration in growth hormone transgenic mice.

AIMS: Acromegaly [overproduction of growth hormone (GH)] and GH deficiency have both been associated with alterations in autonomic nervous system function. The aim of this study was to investigate autonomic nervous system influence on heart rate (HR) in transgenic mice overexpressing bovine GH (bGH). METHODS: HR and HR variability (HRV) were measured in conscious young (8-13 weeks) and old (5-6 months) female bGH and control mice using telemetry. HR control was studied using antagonists and an agonist of adrenergic and muscarinic receptors. Noradrenaline was measured in plasma, heart and kidney using high performance liquid chromatography. RESULTS: Average 24 h resting HR did not differ between bGH and control mice. After saline injection and after muscarinic blockade with methylscopolamine HR increase was blunted (in old) or absent (in young) bGH mice compared with control mice (P < 0.05). Phenylephrine caused a baroreflex mediated decrease in HR from around 550 to 300-350 beats min(-1), not different between bGH and control mice. Time- and frequency-domain measures of HRV were reduced in old bGH compared with control mice (P < 0.05). Noradrenaline concentrations were reduced by 25-49% in plasma and tissue of bGH compared with control mice (P < 0.05). CONCLUSION: The current study suggests reduced autonomic modulation of HR in bGH transgenic mice. Thus, GH appears to have marked effects on autonomic tone, reducing sympathetic nervous system function possibly via reduced noradrenaline stores.

Acromegaly↗

PubMed2004

Virtual reality for simulation of radiographic projections: validation of projection geometry.

OBJECTIVE: To develop a software for virtual reality (VR) simulation of X-ray images based on perspective projections through a patient model derived from data from a CT examination and to evaluate the accuracy in the projection geometry obtained by the software. METHODS: A VR software was developed on a personal computer, with models of a patient, an X-ray machine and a detector. The model of the patient was derived from data from a CT examination of a dry skull. Simulated radiographic images of the patient model could be rendered as perspective projections based on the relative positions between the models. The projection geometry of the software was validated by developing an artificial CT data set containing high attenuation points as objects to be imaged. The accuracy in projection geometry was evaluated in a systematic way. The distances between two dots, representing the projected test points in the simulated radiographic images, were measured. They were compared with theoretical calculations of the corresponding distances using traditional mathematical tools. RESULTS: The difference between the simulated and calculated projected distances never exceeded 0.5 mm. The error in simulated projected distances was in most cases within 1%. No systematic errors were revealed. CONCLUSION: The software, developed for personal computers, can produce simulated X-ray images with high geometric accuracy based on perspective projections through a CT data set. The software can be used for simulation of radiographic examinations.

Computer Simulation↗

PubMed2004

Environmental changes in the North Atlantic Region: SCANNET as a collaborative approach for documenting, understanding and predicting changes.

The lands surrounding the North Atlantic Region (the SCANNET Region) cover a wide range of climate regimes, physical environments and availability of natural resources. Except in the extreme North, they have supported human populations and various cultures since at least the end of the last ice age. However, the region is also important at a wider geographical scale in that it influences the global climate and supports animals that migrate between the Arctic and all the other continents of the world. Climate, environment and land use in the region are changing rapidly and projections suggest that global warming will be amplified there while increasing land use might dramatically reduce the remaining wilderness areas. Because much of the region is sparsely populated--if populated at all--observational records of past environmental changes and their impacts are both few and of short duration. However, it is becoming very important to record the changes that are now in progress, to understand the drivers of these changes, and to predict future consequences of the changes. To facilitate research into understanding impacts of global change on the lands of the North Atlantic Regions, and also to monitor changes in real time, an EU-funded network of research sites and infrastructures was formed in 2000: this was called SCANNET--SCANdinavian/North European NETwork of Terrestrial Field Bases. SCANNET currently consists of 9 core sites and 5 sites within local networks that together cover the broad range of current climate and predicted change in the region. Climate observations are well replicated across the network, whereas each site has tended to select particular environmental and ecological subjects for intensive observation. This provides diversity of both subject coverage and expertise. In this paper, we summarize the findings of SCANNET to-date and outline its information bases in order to increase awareness of data on environmental change in the North Atlantic Region. We also identify important gaps in our understanding and identify where the roles of existing infrastructures and activities represented by SCANNET can facilitate future research, monitoring and ground-truthing activities.

Agriculture↗

PubMed2003

A novel selection system for potato transformation using a mutated AHAS gene.

Acetohydroxyacid synthase (AHAS) is the target enzyme for a number of herbicides. A S653N mutation in the AHAS gene results in an increased tolerance to imidazolinone herbicides. We have investigated the use of the mutated gene as selection gene for potato transformation. This resulted in a transformation system with a very high transformation frequency and low rate of escapes. The mutated AHAS gene was introduced into transformed potato together with a beta-glucuronidase (GUS) gene. Selection on 0.5 microM Imazamox yielded GUS expression in 93-100% of regenerated shoots. Furthermore the mutated AHAS gene was used as selection gene for production of high-amylopectin potato lines. The high transformation frequency was verified and potato lines with the desirable starch quality were obtained.

Acetolactate Synthase↗

PubMed2003

Cancer incidence in airline cabin crew: experience from Sweden.

AIMS: To determine the cancer incidence in Swedish cabin crew. METHODS: Cancer incidence of cabin crew at the Swedish Scandinavian Airline System (SAS) (2324 women and 632 men) employed from 1957 to 1994 was determined during 1961-96 from the Swedish National Cancer Register. The cancer incidence in cabin crew was compared with that of the general Swedish population by comparing observed and expected number of cases through standardised incidence ratios (SIR). A nested case-control study was performed, including cancer cases diagnosed after 1979 and four controls per case matched by gender, age, and calendar year. RESULTS: The SIR for cancer overall was 1.01 (95% CI 0.78 to 1.24) for women and 1.16 (95% CI 0.76 to 1.55) for men. Both men and women had an increased incidence of malignant melanoma of the skin (SIR 2.18 and 3.66 respectively) and men of non-melanoma skin cancer (SIR 4.42). Female cabin attendants had a non-significant increase of breast cancer (SIR 1.30; 95% CI 0.85 to 1.74). No clear associations were found between length of employment or cumulative block hours and cancer incidence. CONCLUSIONS: Swedish cabin crew had an overall cancer incidence similar to that of the general population. An increased incidence of malignant melanoma and non-melanoma skin cancer may be associated with exposure to UV radiation, either at work or outside work. An increased risk of breast cancer in female cabin crew is consistent with our results and may in part be due to differences in reproductive history.

Adult↗

PubMed2003

Activity and protein expression of Na+/K+ ATPase are reduced in microvillous syncytiotrophoblast plasma membranes isolated from pregnancies complicated by intrauterine growth restriction.

In contrast to classical transporting epithelia, the Na(+)/K(+) ATPase is distributed to both the microvillous membrane (MVM) and the basal membrane (BM) of the placental syncytiotrophoblast. Na(+)/K(+) ATPase is important in maintaining the electrochemical gradient for Na(+), which represents the driving force for Na(+)-coupled transport of nutrients. We hypothesized that syncytiotrophoblast Na(+)/K(+)-ATPase activity is reduced in intrauterine growth restriction (IUGR). We isolated MVM and BM from control (n = 10) and IUGR placentas (n = 11). The protein expression of Na(+)/K(+)-ATPase alpha(1)-subunit was determined by Western blotting and found to be slightly reduced in MVM isolated from IUGR (-10%; P < 0.05) placentas. Na(+)/K(+) ATPase activity was measured as the ouabain-sensitive, K(+)-dependent cleavage of the fluorescent pseudosubstrate 3-O-methylfluorescein phosphate and was reduced by 35% in MVM obtained from IUGR placentas (P < 0.02). To assess the transcriptional levels of Na(+)/K(+)-ATPase mRNA, real time PCR was used. No significant changes in steady state mRNA levels for Na(+)/K(+)-ATPase were detected. The expression of the Na(+)/K(+)-ATPase alpha(1)-subunit and Na(+)/K(+)-ATPase activity in the BM were unaffected in cases of IUGR. These data suggest that Na(+)/K(+)-ATPase activity is reduced in the MVM of placentas from IUGR pregnancies. These changes might impair the function of Na(+)-coupled transporters and contribute to the reduced growth of these fetuses.

Case-Control Studies↗

PubMed2002

Humoral immune response against Borna disease virus (BDV) in experimentally and naturally infected cats.

In order to investigate the peripheral and intracerebral humoral immune response against Borna disease virus (BDV) in cats, serum and cerebrospinal fluid (CSF) samples from experimentally and naturally BDV-infected cats were analysed in two different test systems (indirect enzyme-linked immunosorbent assay and indirect immunofluorescent test). The experimentally infected cats developed high antibody titres against the major immunogenic BDV-proteins, p24 and p40. In contrast, the naturally infected cats showed a comparatively weak humoral immune response. The experimentally infected cats were inoculated with either BDV laboratory strain V or a feline BDV-isolate. Some differences existed between the two groups of cats. The former group developed a higher response against p40, whereas the latter group showed, beside the p40-response, a more pronounced p24-response, similar to the situation in the naturally infected cats.

Animals↗

PubMed2002

Neurohormonal influences on maintenance and reversal of two-kidney one-clip renal hypertension.

The factors involved in maintenance and reversal of mean arterial blood pressure (MAP) in the chronic two-kidney one-clip hypertensive rat (2K1C-RHR) are still debated. The reduction in MAP after reversal of 2K1C hypertension has been ascribed either to release of a renal medullary depressor hormone (RMDH) or suppression of the renin-angiotensin and/or sympathetic nervous system. We studied in conscious rats: (i) The effects of angiotensin II receptor blockade (ARB; candesartan), sympathetic blockade (propranolol and phentolamine) or a combination on MAP in 6-week long 2K1C-RHR; (ii) The effects of reversal of 2K1C hypertension by removal of the constricting clip (unclipping, UC) or nephrectomy (Nx) on MAP, plasma renin activity (PRA) and noradrenaline (NA) spillover rates. The results show that: (i) MAP in the 2K1C-RHR was almost normalized by ARB but not significantly affected by the sympathetic blockade. The combination was not more effective than ARB alone; (ii) UC and Nx reduced MAP in 2K1C to similar levels as ARB. No significant changes in PRA or catecholamines could be detected in UC and Nx groups. We conclude that hypertension in 2K1C-RHR is maintained by the renin-angiotensin system without much contribution from the sympathetic nervous system. Furthermore, we found no evidence that UC of our model of 2K1C was associated with a generalized decrease in sympathetic tone or substantial release of RMDH from the unclipped kidney. Thus, we conclude that in the present model of 2K1C, both maintenance and reversal of hypertension are controlled by the renin-angiotensin system.

Angiotensin II↗

PubMed2002

Myelin protein P0-specific IgM producing monoclonal B cell lines were established from polyneuropathy patients with monoclonal gammopathy of undetermined significance (MGUS).

Monoclonal expansion of B cells and plasma cells, producing antibodies against 'self' molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenström's macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P0, using beads coated with P0. P0-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein--Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P0 antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5+ positive, although the expression declined in vitro over time. The anti-P0 antibodies were of IgM-lambda type. The antibodies belonged to the VH3 gene family with presence of somatic mutations. The IgM reacted with P0 and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5+ clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P0-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation.

Aged↗

PubMed2002

Regulation of placental transfer: the Na(+)/H(+) exchanger--a review.

This review article considers the purposes and mechanisms of regulation of placental transfer in general terms and then illustrates some key points with reference to the Na(+)/H(+) exchanger (NHE), a transport protein found in the syncytiotrophoblast. NHE probably has a role in the homeostasis of syncytiotrophoblast intracellular pH and may also be involved in syncytiotrophoblast cell volume regulation as well as H(+) loss from and Na(+) transfer to the fetus. The activity and expression of NHE in the microvillous plasma membrane of the syncytiotrophoblast is reduced in placentas from preterm, growth restricted babies as compared to their gestationally matched normally grown counterparts. There are differential effects of gestation in normal pregnancy on NHE mRNA, NHE protein and NHE activity. There is also evidence of acute modulation of NHE activity. Regulation of NHE in syncytiotrophoblast is therefore complex with control at transcription, post transcription and post translational loci.

Adult↗

PubMed2002

Na(+)/K(+)-ATPase activity and expression in syncytiotrophoblast plasma membranes in pregnancies complicated by diabetes.

Many of the transport processes across the syncytiotrophoblast (ST), such as amino acid transport, are Na(+)-coupled. The maintenance of a low intracellular Na(+) concentration by Na(+)/K(+)-ATPase is therefore crucial for placental transport of nutrients and consequently, foetal growth. In pregnancies complicated by diabetes foetal growth is often accelerated despite rigorous glycemic control of the mother, however the underlying mechanisms are not fully understood. We tested the hypothesis that Na(+)/K(+)-ATPase in ST plasma membranes is up-regulated in diabetic pregnancies associated with accelerated growth. ST microvillous (MVM) and basal (BM) plasma membranes were purified from term placentas of normal pregnancies (control, n=13) and pregnancies complicated by insulin-dependent diabetes mellitus (n=7) or gestational diabetes (n=6). All mothers with diabetes gave birth to large for gestational age babies. The Na(+)/K(+)-ATPase alpha(1)-subunit protein expression (Western blot) in MVM and BM was unaltered by diabetes. Na(+)/K(+)-ATPase activity (K(+)-stimulated, ouabain-sensitive phosphatase activity) in ST plasma membranes was not affected by diabetes. This is the first study of Na(+)/K(+)-ATPase in ST membranes of the human placenta in diabetes. Our data show that accelerated foetal growth in diabetic pregnancies is not associated with elevated ST Na(+)/K(+)-ATPase protein expression or activity.

Adult↗

PubMed2002

Quantitative relationships between pigment-related mRNA and biochemical melanoma markers in melanoma cell lines.

The use of reverse transcription polymerase chain reaction (RT-PCR) analysis of melanoma-specific transcripts for the identification of circulating melanoma cells has shown very variable results in different studies on melanoma patients. We have therefore developed quantitative methods to study both analytical and biological variations as possible causes of this phenomenon. Pigment-related and S-100 beta transcripts were quantified in 12 different melanoma cell lines and related to the amounts of 5-S-cysteinyldopa, pigment and S-100B protein. A real-time PCR method was used and the results were expressed as absolute number of transcripts per cell. Tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2 and MART-1/Melan-A mRNA varied from undetectable (< 10(-4) transcripts/cell) to 10(3) transcripts/cell, i.e. by a factor > 10(7) in the different cell lines. S-100 beta mRNA varied from 2.8 to 165 transcripts/cell, i.e. by a factor of 60. Tyrosinase, TRP-1 and TRP-2 mRNA correlated significantly with the amount of 5-S-cysteinyldopa, an intermediate pigment metabolite (P < 0.001, P < 0.001 and P < 0.01, respectively). The amount of S-100 beta mRNA correlated significantly with the amount of S-100B protein (P < 0.001). No cross-correlations were seen between the pigment-related and S-100-related analytes. We conclude that one reason behind the negative results of RT-PCR measurement of pigment-related mRNA may be that these transcripts are not always expressed in the particular cells present in the patient's blood. Furthermore, variation in the expression of the order of 10(7) must have great impact on the diagnostic sensitivity. Measurement of S-100 beta mRNA would be more sensitive, but the use of this transcript is hampered by its presence in the blood cells.

Antigens, Neoplasm↗

PubMed2002

Activity and protein expression of the Na+/H+ exchanger is reduced in syncytiotrophoblast microvillous plasma membranes isolated from preterm intrauterine growth restriction pregnancies.

Regulation of syncytiotrophoblast intracellular pH is critical to optimum enzymatic and transport functions of the placenta. Previous studies of Na(+)/H(+) exchanger (NHE) activity in the placenta from pregnancies complicated by intrauterine growth restriction (IUGR) have produced conflicting results. The possible role of altered placental pH regulation in the development of acidosis in some fetuses subjected to IUGR remains to be fully established. We investigated the activity and protein expression of the NHE in syncytiotrophoblast microvillous (MVM) plasma membranes isolated from preterm and term placentas obtained from uncomplicated and IUGR pregnancies. Western blotting showed that the expression of NHE isoforms 1, 2, and 3 was approximately 10-fold greater in MVM than in basal plasma membrane (BM). Immunohistochemistry localized NHE-1 and NHE-2 to MVM and BM and NHE-3 to the MVM, BM, and cytoplasm of the syncytiotrophoblast. NHE-1 expression in MVM from preterm IUGR placentas was reduced by 55%, compared with gestational age-matched controls (P < 0.05, n = 6 and n = 16, respectively), whereas NHE-1 expression was unaltered in term IUGR placentas (n = 8). The activity (amiloride-sensitive Na(+) uptake) of NHE in MVM from IUGR preterm placentas was reduced by 48% (P < 0.05, n = 6). In contrast, MVM NHE activity was unchanged in term IUGR (n = 7). Using Northern blotting, no difference could be demonstrated in NHE-1 mRNA expression between IUGR and control groups. The reduced activity and expression of NHE in MVM of preterm IUGR placentas may compromise placental function and may contribute to the development of fetal acidosis in preterm IUGR fetuses.

Blotting, Northern↗