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Biomedical subjects

M Olsson

Publications and source records attributed to M Olsson.

At least 91 records · Page 5Linked to original sources

Quality of life in octogenarians after valve replacement due to aortic stenosis. A prospective comparison with younger patients.

BACKGROUND: Results of aortic valve surgery in octogenarians have been evaluated as event-free survival. However, little attention has been given to quality of life aspects. METHODS: Thirty-two consecutive patients, mean age 83 +/- 2 years, undergoing valve replacement due to aortic stenosis, were compared to 30 patients, mean age 71 +/- 3 years, undergoing the same procedure. Mortality, morbidity and quality of life were studied. An interview was performed before surgery and 3 and 12 months postoperatively. The questionnaire contained items related to self-rated health, symptoms, physical ability, sleep disturbances and social and emotional functioning. RESULTS: Pre-operatively the older patient group was in a worse condition with a higher NYHA functional class and a more pronounced cardiomegaly. They had more cardiac symptoms and were more depressed. The control group had a higher score for physical ability and rated their quality of life as better. Postoperatively there was a higher early mortality rate in the octogenarians (9% vs 0%; ns). After 3 months, improvement of functional status and relief of symptoms was observed in both groups. Physical ability improved and the depression score decreased significantly in both groups. Self-rated health and quality of life improved. One year after valve replacement the improvement in quality of life was of a similar magnitude in the two groups. CONCLUSION: Following aortic valve replacement, octogenarians, despite a more compromised pre-operative status showed an improvement in symptomatology, physical ability and general well being, of a similar magnitude to that of the younger patients group. These findings lend further support to the recommendation that valve replacement should be performed in octogenarians with symptomatic aortic stenosis.

Aged↗

Detection of Pneumocystis carinii DNA by filtration of air.

The high incidence of pneumonia caused by Pneumocystis carinii in immunosuppressed patients makes it the most important parasite in non-tropical geographical regions. It has recently been shown to be a fungus, but several aspects of this organism are still poorly understood. A major question of clinical relevance is the nature of transmission and, thereby, the related problem of prevention. The mode of P. carinii transmission is thought to be air, but this is based on circumstantial evidence, the transmissive stage has not been identified. We attempted to capture P. carinii by filtration of air in the vicinity of cages containing P. carinii infected Wistar rats. Using nested polymerase chain reaction amplification of the thymidylate synthase gene to demonstrate P. carinii we were able to demonstrate P. carinii DNA on such filters. This strongly supports the suggested mechanism of transmission of Pneumocystis by means of airborne spores and suggests an approach to their isolation and characterization.

Air Microbiology↗

A rapid and simple nested PCR assay for the detection of Pneumocystis carinii in sputum samples.

Detection of Pneumocystis carinii by the polymerase chain reaction (PCR), based on the thymidylate synthase (TS) gene of rat P. carinii, is a specific and sensitive method for the detection of the parasite in respiratory samples. However, the use of the method is limited by a laborious phenol-chloroform DNA extraction method and an expensive and time-consuming hybridization procedure. For routine clinical samples, DNA preparation can be simplified and hybridization substituted by a nested PCR technique. Such a modified PCR procedure, based on the TS gene of P. carinii, was evaluated on 190 induced sputum samples from 50 immunosuppressed patients, infected with human immunodeficiency virus (HIV), with and without symptoms of P. carinii pneumonia (PCP). The PCR assay, preceded by a rapid DNA preparation (Wizard DNA Clean-up), detected P. carinii-DNA in 13/15 sputa containing parasites as seen by microscopy using immunocytochemical (IFL) staining, and in 10 additional sputum samples lacking demonstrable parasites by microscopy. These samples are to be considered as 'true' positives, since all but 2 were from patients, who developed a PCP within 1 year. We conclude that the nested PCR assay is more sensitive than IFL for the detection of P. carinii in AIDS patients, prior to the debut of PCP symptoms.

Animals↗

Influence of dolichol on microsomal membrane functions.

Microsomal membranes from rat liver were extracted with n-pentane in order to remove the lipid products of the mevalonate pathway, dolichol, ubiquinone and cholesterol. Dolichol and cholesterol were subsequently reincorporated into these extracted membranes. Electron microscopic examination demonstrated that extraction did not alter the vesicular membrane structure of the microsomes. The extracted vesicles were permeable to uncharged molecules in the same manner as control microsomes but had an increased permeability for charged molecules. Enzyme denaturation was not observed. The contraction of extracted vesicles was greatly increased when the incubation medium was supplemented with non-penetrating compounds such as polyethylene glycol and was much greater than that of control microsomes. When extracted membranes were reconstituted with dolichol or cholesterol, the original lower degree of contraction was reestablished. The effects of dolichol reincorporation on a number of microsomal enzyme activities were investigated and some limited changes were observed. These results demonstrate that extraction of microsomes with n-pentane and subsequent reincorporation of dolichol is an effective approach for investigating the functions of this lipid. Dolichol and cholesterol both affect microsomal membrane fluidity, but only cholesterol modifies the activities of certain integral microsomal membrane enzymes to a larger extent.

Animals↗

Preservation of fetal ventral mesencephalic cells by cool storage: in-vitro viability and TH-positive neuron survival after microtransplantation to the striatum.

Preservation of fetal ventral mesencephalic (VM) dopaminergic tissue prior to transplantation has been hampered by the fact that the cells are vulnerable to mechanical and osmotic stress after storage. Previous quantitative studies have shown that cool storage in a so-called 'hibernation medium' prior to grafting, can be used safely for up to 2 days without morphological or functional losses [16,32] using standard transplantation techniques. In the present study on rat fetal VM tissue we have investigated (i) the accuracy of different vital stains (trypan blue exclusion and ethidium bromide stain) to predict in vivo viability of VM cell suspensions after grafting; (ii) the influence of different storage media (glucose-saline, HBSS, DMEM, CO2-independent medium and hibernation medium), temperatures (+4 degrees C or +21 degrees C) and preparations (cell suspension or intact pieces) on the viability scores and total number of cells in vitro; and (iii) the survival and functional effects of intrastriatally grafted VM tissue after preservation by cool storage for up to 12 days using a less traumatic microtransplantation technique. The results show that cool storage at +4 degrees C of intact VM pieces in hibernation medium gives the best in vitro viability scores. Microtransplantation of cell suspensions prepared from cool-stored VM tissue produced good survival of tyrosine hydroxylase (TH)-positive graft neurons for up to 8 days of storage, and functional compensation in the amphetamine-rotation test for up to 12 days of storage. The total yield of surviving TH-positive neurons was unchanged, compared to fresh grafts, after 5 and 8 days of storage, and only reduced by 48% in the grafts stored for 12 days prior to implantation. These findings highlight the potential usefulness of a combination of cool storage and microtransplantation techniques to be able to extend the preservation periods of VM tissue. Such procedures may ultimately help to increase the safety and flexibility in experimental and clinical studies on neural transplantation of dopaminergic neurons.

Animals↗

The GTPase activity of the Escherichia coli Ffh protein is important for normal growth.

The Escherichia coli (E. coli) Ffh protein is homologous to the 54kDa subunit of the eukaryotic signal recognition particle. We have examined an intrinsic GTPase activity of this protein and have created mutations in one sequence motif (GXXXXGK) of the putative GTP binding site. When glycine-112 was changed to valine (Ffh-G112V), Vmax was reduced to only 4% of the wildtype level. On the other hand, when glutamine-109 was altered to glycine (Ffh-Q109G), the major effect was a 50-fold increase in Km. These results show that the residues Q-109 and G-112 are essential for the binding and hydrolysis of GTP and that they are part of a catalytic site structurally related to that of many other GTPase proteins. Expression of the mutant protein Ffh-G112V in E. coli was highly toxic in the presence of the wildtype protein. In contrast, genetic complementation experiments showed that a viable strain could be constructed where the Ffh-Q109G mutant protein replaced wildtype Ffh. However, expression of the mutant protein had a negative effect on growth rate at 30 degrees C and resulted in elongated cells. These results demonstrate that the GTPase activity of the Ffh protein is required for proper function of the protein in vivo.

Amino Acid Sequence↗

Projection neurons in fetal striatal transplants are predominantly derived from the lateral ganglionic eminence.

In the present study, we have characterized aspects of integration, growth and phenotypic differentiation of embryonic grafts derived from the selective dissection of either the lateral or medial portion of the ganglionic eminences of the rodent forebrain. Donor tissues were derived from embryonic day 15 rat, or embryonic day 14 mouse embryos, and injected, as single cell suspensions into the striatum or substantia nigra of adult rats previously subjected to an intrastriatal ibotenic acid lesion. Two to six weeks following grafting, immunocytochemical detection of DARPP-32, the 32,000 mol. wt dopamine- and cyclic AMP-regulated phosphoprotein, was used to identify areas with a striatum-like phenotype within both the intrastriatal and the intranigral grafts. It was thus revealed that all the lateral ganglionic eminence grafts, irrespective of their placement, were dominated by striatum-like tissue (up to 90% of the total graft volume), while the medial ganglionic eminence transplants were only sparsely positive (< 10% of the total graft volume). These striatum-like regions of the grafts were selectively innervated by tyrosine hydroxylase immunopositive fibres from the host substantia nigra. Furthermore, axons derived from the lateral ganglionic eminence mouse grafts placed in the striatum, as detected by the mouse-specific neuronal marker M6, showed a more extensive and directed outgrowth towards the globus pallidus when compared to fibres emanating from the medial ganglionic eminence grafts. Mouse lateral and medial ganglionic eminence grafts placed into the substantia nigra exhibited similar fibre outgrowth patterns; both types of grafts thus innervated the substantia nigra-pars reticulata and extended axons into the cerebral peduncle. These results show that DARPP-32-positive striatal projection neurons are derived, for the most part, from the lateral ganglionic eminence and that the restricted lateral ganglionic eminence dissection provides a more optimal source of striatal tissue for grafting in the rat Huntington model.

Animals↗

Regional incorporation and site-specific differentiation of striatal precursors transplanted to the embryonic forebrain ventricle.

The developmental potential of neural progenitors derived from the E13.5-E14 lateral or medial ganglionic eminences (LGE and MGE, respectively) or the E12 ventral mesencephalon (VM) was examined in cross-species transplantation model. After injection into the E15 rat forebrain ventricle, mouse LGE progenitors (unlike those of the MGE or VM) were consistently integrated into the host striatum, expressing neurochemical phenotypes and axonal projections characteristic of striatal projection neurons. Additionally, both LGE and MGE precursors displayed widespread incorporation into distinct forebrain and midbrain structures, whereas the more caudally derived VM cells were largely confined to midbrain structures. These results suggest that many LGE precursors are positionally specified for striatal incorporation, while a portion also possess greater potential reflected in more widespread integration following intraventricular injection.

Animals↗

Bridges supported by free-standing implants versus bridges supported by tooth and implant. A five-year prospective study.

The clinical question at issue, whether it is possible to combine implants and natural teeth via fixed bridges, is of current interest. The treatment of the subjects of this prospective study was performed between June 1984 and December 1986. This article presents the 5-year results of the study. The consecutive patient material comprised 23 patients with Applegate Kennedy Class I residual dentition in the mandible and a complete maxillary denture. All 23 patients were provided with implants ad modum Brånemark in each mandibular quadrant. One side was randomized to rehabilitation with fixed bridge between the distal tooth of the residual dentition and an implant; the other side received a free-standang bridge on 2 implants. The fixture survival rate was 88%. No difference was found between the two sides. Bridge stability was 89% for the implant bridges and 91% for the combination bridges. The change in marginal bone level at the implants was small during the 5-year follow up period (on average 0.1-0.3 mm) and with no difference between the two sides. In conclusion, it was not possible to demonstrate any higher risk of implant or prosthetic failure for tooth-implant fixed bridges compared with implant-supported bridges.

Alveolar Bone Loss↗

Mandibular function before and after orthodontic treatment.

To determine the influence of orthodontic treatment on mandibular function, a longitudinal study was initiated on 245 consecutive prospective orthodontic patients before and after the orthodontic treatment. Of the 245 referred patients, eight declined treatment and 27 moved to other parts of the country before the treatment was completed. Thus, the longitudinal study was based on 210 patients. The functional examination was made according to Carlsson and Helkimo (1972) and Helkimo (1974), and by the same person (MO). Before the orthodontic treatment, symptoms of temporomandibular disorders (TMD) were found in 16.7 per cent of the patients and in 6.7 per cent after treatment. The number of subjects without signs or symptoms of TMD increased from 26.7 per cent before treatment to 46.2 per cent after. According to the dysfunction index (Helkimo, 1974), 31.4 per cent of the patients had a moderate and 13.8 per cent a severe mandibular dysfunction before the start of orthodontic treatment. After the treatment, the corresponding figures were 14.3 and 5.7 per cent, respectively. The material was divided into groups, consisting of boys and girls younger than 13 years, and 13 years and older at the start of treatment. Before treatment there was a higher prevalence of signs and symptoms of TMD in the older age group than in the younger, and higher in girls than in boys. After the orthodontic treatment, the prevalence was still higher in girls than in boys in both age groups, but not higher in the older age group than in the younger group.

Adolescent↗

Forelimb akinesia in the rat Parkinson model: differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test.

Methods for the assessment of akinesia in the unilateral rat Parkinson model have so far been lacking. The experiments reported here evaluate the usefulness of a new "stepping test" to monitor forelimb akinesia in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the mesencephalic dopamine (DA) system, and to assess the ability of DA-receptor agonists and fetal DA neuron transplants to reverse these deficits. The 6-OHDA lesion induced marked and long-lasting impairments in the initiation of stepping movements with the contralateral paw. Systemic injections of low doses (chosen to be subthreshold for induction of rotation) of the mixed D1 and D2 receptor agonist apomorphine, the D1-selective agonist SKF 38393, and to a lesser extent also the D2-selective agonist quinpirole were effective in reversing these deficits. Similar effects was seen after a subrotational dose of L-dopa, whereas amphetamine had no effect. Fetal nigral transplants, implanted as multiple deposits in the ipsilateral caudate-putamen and substantia nigra, restored initiation of stepping to a similar degree as the DA agonists. Nigral grafts placed in substantia nigra alone were also effective, although the improvement was less pronounced. Apomorphine, at a dose effective in the lesion-only animals, had no additive effect in the grafted rats, whereas amphetamine appeared to further improve stepping in the rats with intranigral transplants. Identical experiments were performed on skilled forelimb use in the so-called staircase test. Interestingly, neither the DA agonist drugs nor the nigral transplants had any effects on the lesion induced deficits in this more complex task. The results show that forelimb stepping is a highly useful test to monitor lesion-/and transplant-induced changes in forelimb akinesia, a behavioral parameter that may be analogous to limb akinesia and gait problems seen in patients with Parkinson's disease.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Diseases and environmental contaminants in seals from the Baltic and the Swedish west coast.

Investigations have shown that Baltic grey seal (Halichoerus grypus) and ringed seal (Phoca hispida) suffer from a disease complex described as a primary lesion in the adrenals causing secondary reactions in various other organs. Studies on historical Baltic grey seal skull bone material show that the prevalence of affected animals started to increase after World War II. The disease complex explains the dramatic decrease in the Baltic grey and ringed seal population during the 1960s and 1970s and is believed to be caused by environmental pollutants. In 1988, about 60% of the harbor seal population (Phoca vitulina) along the Swedish west coast and in the southwestern part of the Baltic died in the PDV epizootic (Phocine Distemper Virus). Whether the course of the epizootic was altered by environmental pollutants is still an open question. Studies on historical harbor seal skull bone material from both the Baltic and the Swedish west coast show that the incidence of skull bone lesions has also increased in these populations since World War II, indicating the presence of unnatural stress factors. After the epizootic, the harbor seal populations both in the Baltic and along the Swedish west coast have increased in number. Chemical analysis of tissues has been performed on the three seal species collected in various areas of the Baltic and the Swedish west coast. The concentrations of 17 metals and non-metal elements, sDDT and PCBs, DDE and PCB methylsulfones, toxaphene, chlordanes, polybrominated diphenyl ethers, PCDDs and PCDFs have been determined in selected groups of seals in order to determine spatial, species and age variations in concentrations. Furthermore, healthy animals have been compared to diseased animals. Spatial variation was found mostly within the group of organohalogenated compounds, a group of contaminants where a strong covariation between the various compounds was also found. On the basis of the analytical results as well as the pathological findings on Baltic seals, the group of DDE and PCB methyl sulfones is tentatively suggested to be more important in explaining the disease complex than coplanar structures including dioxins.

Adrenal Gland Diseases↗

Release of 5'-terminal deoxyribose-phosphate residues from incised abasic sites in DNA by the Escherichia coli RecJ protein.

Excision of deoxyribose-phosphate residues from enzymatically incised abasic sites in double-stranded DNA is required prior to gap-filling and ligation during DNA base excision-repair, and a candidate deoxyribophosphodiesterase (dRpase) activity has been identified in E. coli. This activity is shown here to be a function of the E. coli RecJ protein, previously described as a 5'-->3' single-strand specific DNA exonuclease involved in a recombination pathway and in mismatch repair. Highly purified preparations of dRpase contained 5'-->3' exonuclease activity for single-stranded DNA, and homogeneous RecJ protein purified from an overproducer strain had both 5'-->3' exonuclease and dRpase activity. Moreover, E. coli recJ strains were deficient in dRpase activity. The hydrolytic dRpase function of the RecJ protein requires Mg2+; in contrast, the activity of E. coli Fpg protein, that promotes the liberation of 5'-->3'Rp residues from DNA by beta-elimination, is suppressed by Mg2+. Several other E. coli nucleases, including exonucleases I, III, V, and VII, endonucleases I, III and IV and the 5'-->3' exonuclease function of DNA polymerase I, are unable to act as a dRpase. Nevertheless, E. coli fpg recJ double mutants retain capacity to repair abasic sites in DNA, indicating the presence of a back-up excision function.

Apurinic Acid↗

A microtransplantation approach for cell suspension grafting in the rat Parkinson model: a detailed account of the methodology.

Shortcomings of current techniques used for the intracerebral transplantation of ventral mesencephalic dopamine neurons include low graft survival, high variability, considerable implantation trauma and suboptimal graft integration. In order to overcome these limitations, we have adopted a microtransplantation approach which allows precise and reproducible implantation of ventral mesencephalon cell suspensions at single or multiple sites with minimal trauma and improved survival and integration of the grafted neurons [Nikkhah et al. (1994) Brain Res. 633, 133-143]. The present study was undertaken to determine the influence of different grafting parameters as well as the time-course of development of micrografted dopaminergic neurons and to devise an optimal microtransplantation procedure in the rat Parkinson model, Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway received four graft deposits of either 0.25, 0.5, 1.0 or 2.0 microliters along four injection tracts (150,000 cells/microliters) using either a glass capillary (o.d. 50-70 microns) or a regular cannula (o.d. 0.50 mm, metal cannula grafts). At one, two and 12 weeks postgrafting (capillary grafts) and at 12 weeks postgrafting (metal cannula grafts) dopamine neuron survival and graft volumes were measured and the implantation trauma assessed by glial fibrillary acidic protein expression. The results demonstrate that single deposits of 50,000-75,000 cells in 0.5 microliter, implanted with a glass capillary, provide the best environment both for dopaminergic and non-dopaminergic neuron survival. Grafts implanted with the glass capillary showed much weaker long-term glial fibrillary acidic protein expression along the injection tract and around the implants than was the case in grafts implanted with the thicker metal cannula. Optimal graft integration and minimal disturbances of host brain structures can reliably be achieved by small-sized implants (20,000-35,000 cells/deposit). Tyrosine hydroxylase-positive fiber outgrowth from micrografted dopaminergic neurons was seen not only in the surrounding caudate-putamen, but also along white matter tracts into the nucleus accumbens and the overlying cerebral cortex. Spreading of dopaminergic micrografts over multiple small deposits rather than increasing the volume of single grafts gave more extensive reinnervation of the entire host striatum. The micrografting technique provides a useful tool to improve graft-host interactions in the rat Parkinson model, and it allows more precise and reproducible quantitative studies on dopamine neuron survival and growth in intrastriatal ventral mesencephalon transplants. This technique should also be highly useful for the intracerebral implantation of cells derived from primary cultures or cell lines [Gage and Fisher (1991) Neuron 6, 1-12].

Animals↗