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Biomedical subjects

L Eriksson

Publications and source records attributed to L Eriksson.

At least 145 records · Page 8Linked to original sources

GABA-transaminase activity in rat and human brain: regional, age and sex-related differences.

The activity of 4-aminobutyrate:2-oxoglutarate transaminase (GABA-T) has been investigated in the rat and human brain. Both rat and human brain GABA-T retained its full activity for at least 2 months and with a loss of less than 10% after 6 months when frozen at -20 degrees C as tissue parts. There was a loss of activity of mouse brain GABA-T of about 15% per 24 hours postmortem. In the rat brain, GABA-T activity varied from low values in cortex and hippocampus to high in brain stem and cerebellum. There was a significant increase of GABA-T activity with age from 1 to 6 weeks and a significant reduction of the activity with age thereafter. Male rats had significant higher activity than female rats. In the human brain, GABA-T activities were measured in twelve regions of autopsied brains from 10 adult control subjects. No difference was found between the activities in the left and right sides. There is considerable variation in enzyme activity across the brain, with low activities in e.g. pons and medulla oblongata and high activities in e.g. caudatus, substantia nigra and hypothalamus. The activity of the enzyme is significantly different both between brain regions and between individuals.

4-Aminobutyrate Transaminase↗

Osseous and muscular changes after vertical ramus osteotomy. A magnetic resonance imaging study.

Magnetic resonance (MR) imaging was performed about 2 years after vertical ramus osteotomy of 10 patients to study changes in the mandibular condyle, cortical and cancellous bone of the proximal fragment, and muscles of mastication. MR imaging observations of the surgically treated patients were compared with findings in 10 asymptomatic untreated control subjects. The results showed that the MR appearance of bone marrow of the mandibular condyle was normal in all patients and in all control subjects. No MR evidence of avascular necrosis of the mandibular condyle was found. MR imaging artifacts from microscopic metallic particles were seen in all surgically treated regions. Thickening of the buccal and lingual cortical bone with narrowing of the bone marrow space was seen bilaterally in eight patients and unilaterally in two patients. Slight medial tipping of the mandibular condyle was seen unilaterally in two patients. Atrophic changes with decreased muscle volume and fatty replacement of muscle tissue was seen unilaterally in eight patients. None of these alterations were seen in the control subjects. MR imaging appears to be an excellent method to study morphologic changes of the muscles of mastication and osseous fragments after orthognathic surgery of the mandible. Thickening of the cortical bone and narrowing of the bone marrow space of the proximal fragment was frequently seen after vertical ramus osteotomy of the mandible and most likely represents remodeling associated with normal healing.

Adolescent↗

Rapid feasibility studies of tracers for positron emission tomography: high-resolution PET in small animals with kinetic analysis.

The development of methods for production of a radiotracer for use in human studies with positron emission tomography (PET) is often a time-consuming process of optimizing radiolabelling yields and handling procedures. Sometimes the radiotracer is not the original drug, but rather a derivative with unknown in vivo pharmacological properties. We have developed a fast and simple method of testing putative new PET tracers in vivo in small animals. The procedure has been validated in rats with different PET tracers with known kinetic and pharmacological properties ([2-18F]2-fluoro-2-deoxy-D-glucose, [N-methyl-11C]Ro 15-1788, and [15O]butanol). The tracer concentration in arterial blood was continuously measured to obtain the brain input function. Following image reconstruction of the scans, time-activity curves of selected regions of interest were generated. Estimations of CMRglc (1.0 +/- 0.2 mumol g-1 min-1), CBF (1.4 +/- 0.4 ml g-1 min-1) and transport rate constants for [N-methyl-11C]Ro 15-1788 (K1 = 0.44 +/- 0.01 ml g-1 min-1 and k2 = 0.099 +/- 0.005 min-1) as well as calculated first pass extraction (0.32 +/- 0.1) are in reasonable agreement with literature values. Small animal studies require minimal amounts of radioactivity and can be performed without sterility and toxicology tests. They may serve as a preliminary basis for radiation safety calculations because whole body scans can be performed even with a head scanner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Specification and selection of regions of interest (ROIs) in a computerized brain atlas.

The computerized individually adjustable brain atlas (CBA) has been further developed. The atlas was primarily designed for anatomical localization and quantitative evaluation of data in positron emission tomography (PET), but may also be employed for other neuroimaging modalities, such as transmission computed tomography (CT) and magnetic resonance imaging (MRI). The atlas is based on anatomical information obtained from digitized cryosectioned brains. Using spatially standardized and then averaged MRI images, we demonstrate the high localization accuracy and precision of the brain atlas. This is a prerequisite for obtaining accuracy when using the atlas in the localization and the quantitative evaluation of PET data. The specification and the selection of region of interests (ROIs) by the CBA are presented and discussed.

Brain↗

Storage of saline-adenine-glucose-mannitol-suspended red cells in a new plastic container: polyvinylchloride plasticized with butyryl-n-trihexyl-citrate.

Blood collection and component preparation have been performed in integrally connected multiple plastic containers made with a new plastic. This polyvinylchloride (PVC) container plasticized with butyryl-n-trihexyl-citrate (BTHC) is a new material for blood storage; it contains no di(2-ethylhexyl)phthalate (DEHP). After removal of plasma and buffy coat, the red cells were suspended in saline-adenine-glucose-mannitol (SAGM) medium. After 42-day refrigerator storage, the total adenine nucleotide concentration remained the same as the initial concentration in the red cells, whereas ATP levels had decreased to 61 percent of the initial value. The 2,3 DPG concentration was 62 percent of normal on Day 7 and 21 percent on Day 14. Glucose consumption, lactate production, potassium leakage from red cells, and pH levels were similar to those found after storage in DEHP-plasticized containers under the same conditions. After 42 days, hemolysis levels were 0.56 +/- 0.21 percent and 0.42 +/- 0.17 percent in two series of units mixed weekly and 0.70 +/- 0.27 percent in units stored unmixed. Although even higher levels of hemolysis were observed in the units stored unmixed and used for 24-hour posttransfusion survival, the autologous red cell recovery results were excellent (83.2 +/- 5.1%, n = 8). BTHC-plasticized PVC is found to be a suitable material for 42-day storage of red cells in SAGM solution.

2,3-Diphosphoglycerate↗

White cells protect donor blood against bacterial contamination.

The possible beneficial role of white cells (WBCs) in donor blood has been investigated with respect to their capacity to remove bacteria. Preparations of buffy coat and whole blood, containing as well as reduced of WBCs, were inoculated with Staphylococcus epidermidis, S. aureus, Escherichia coli, Pseudomonas aeruginosa, and Propionibacterium species. Upon storage at room temperature, the presence of WBCs resulted in a reduction of the bacterial content. Units inoculated with S. epidermidis and E. coli were completely cleared of bacteria within 5 to 24 hours. On the other hand, S. aureus, after an initial reduction in number, started to multiply. In WBC-reduced units, the initial bacterial content remained unchanged for 5 hours, but the bacteria then exhibited vigorous growth within 48 hours in buffy coat and slower growth in whole blood. Propionibacterium sp. did not grow with or without WBCs. P. aeruginosa did not grow in buffy coat but showed a growth pattern similar to that of S. aureus in whole blood. The presence of WBCs in the donor blood during the first hours after collection thus seems to rid the blood of at least some species of bacteria. These results indicate that it would be favorable not to perform WBC reduction during blood collection and that several hours of contact can be needed to obtain sterility.

Blood↗

Strain differences in baroreflex inhibition by centrally infused enalapril in old rats.

To determine whether inhibition of the brain renin-angiotensin system would affect baroreflexes similarly in old rats of different strains, we compared 24-month-old male Fischer 344 and Sprague-Dawley rats. Baroreflex sensitivity was tested while the rats were awake by recording reflex heart rate responses elicited as blood pressure was elevated with phenylephrine or lowered with sodium nitroprusside. Sprague-Dawley rats had higher blood pressures and lower heart rates initially. Chronic infusion of enalapril, a converting enzyme inhibitor, into a lateral cerebral ventricle (ICV) for two weeks lowered blood pressure in Sprague-Dawley but not in Fischer 344 rats. Furthermore, reflex bradycardia was unaffected in either rat strain, but reflex tachycardia was selectively suppressed in Fischer 344 rats. Thus, although time controls were not done to rule out spontaneous changes during the 14-day infusion period, these results suggest that central cardiovascular regulation does not change similarly with age in these two rat strains. As removal of the brain renin-angiotensin system lowered blood pressure in one strain and inhibited reflex tachycardia in the other, the divergence could mean that the brain renin-angiotensin system acts differently to keep blood pressure elevated in Sprague-Dawley rats and modulate reflex tachycardia in Fischer 344 rats.

Aging↗

Minimum analogue peptide sets (MAPS) for quantitative structure-activity relationships.

The information contents in previously published peptide sets was compared with smaller sets of peptides selected according to statistical designs. It was found that minimum analogue peptide sets (MAPS) constructed by factorial or fractional factorial designs in physiochemical properties contained substantial structure-activity information. Although five to six times smaller than the originally published peptide sets the MAPS resulted in QSAR models able to predict biological activity. The QSARs derived from a MAPS of nine dipeptides, and from a set of 58 dipeptides inhibiting angiotensin converting enzyme were compared and found to be of equal strength. Furthermore, for a set of bitter tasting dipeptides it was found that an incomplete MAPS of 10 dipeptides gave just as good a model as the model based on a set of 48 dipeptides. By comparison other non-designed sets of peptides gave QSARs with poor predictive power. It was also demonstrated how MAPS centered on a lead peptide can be constructed as to specifically explore the physiochemical and biological properties in the vicinity of the lead. It was concluded that small information-rich peptide sets MAPS can be constructed on the basis of statistical designs with principal properties of amino acids as design variables.

Amino Acid Sequence↗

A multivariate representation and analysis of DNA sequence data.

A new way to represent and analyze DNA sequence data is described. This approach complements methods currently used, in that it allows the systematic part of the variation between different sequences to be modeled. This can prove as informative as absence of variation (homology), which is the most widely used criterion for comparing sequence data. A multivariate sequence-activity model (SAM), for DNA-promoter sequences is presented, by which the relative promoter strength is modeled in terms of the primary DNA-sequence. The model is shown to have a good predictive capability. The coefficients from the model are interpreted, and used to design new structures predicted to be strong promoters in the system investigated. The approach described is also applicable to other kinds of sequence data, e.g. RNAs, proteins or peptides.

Base Sequence↗

A strategy for ranking environmentally occurring chemicals. Part VI. QSARs for the mutagenic effects of halogenated aliphatics.

A strategy for the systematic analysis and priority ranking of environmental chemicals has been applied to a class of 58 halogenated aliphatic hydrocarbons. A training set of ten compounds representing this class, was selected by statistical design. The training set compounds were then subjected to biological testing in the Salmonella typhimurium reverse mutation assay (Ames test). The measured biological data, recorded as dose-response curves, were analyzed to determine the mutagenic potency (slope of the initial portion) and the mutagen dose (MD 50) required to increase the number of revertants above the background by 50%. For each compound, four mutagenic potency estimates and four MD 50 values were determined, all originating from the tester strains TA 100 and TA 1535 with and without metabolic activation. The obtained responses were analyzed with multivariate techniques to give QSAR models relating the mutagenic potency data to the physico-chemical properties of the compounds. Finally, the derived QSARs were used to predict the mutagenic potencies and the MD 50S for the non-tested compounds in the class.

Chemical Phenomena↗

Blood sampling devices and measurements.

Quantitative positron emission tomography requires the determination of the tracer concentration in arterial plasma or full blood as a function of time. This defines the experimental input function. The model prediction, with which the positron camera regional time-activity curves are compared, is given by the experimental input function convoluted with the model. This paper reviews different strategies for determining the input function, invasive techniques, such as manual blood sampling and the use of automated blood sampling systems, and non-invasive techniques. The importance of corrections is discussed, such as accurate cross-calibrations of the different detectors used in quantitative PET and corrections for differences in time phase between the regional PET time-activity curves and the input function. We also report on the use of a PET system in non-invasive determinations of the input function. By imaging the neck region the time-activity curve of the carotid arteries can be obtained. The PET time-activity curves of the carotid arteries are in good agreement with a conventional experimental input function determined from the radial artery with an automated blood sampling system. However, PET time-activity curves of the radial arteries can not be used without a deconvolution since the resistance in the intact radial artery causes dispersion compared to the input function obtained by invasive methods.

Blood Specimen Collection↗

Enhanced sympathetic mediation of chronotropic baroreflexes in old Sprague-Dawley rats.

We compared reflex heart rate responses elicited during intravenous infusions of phenylephrine or sodium nitroprusside in conscious 4- and 24-month-old male Sprague-Dawley rats to determine whether baroreflex regulation changes with age. Underlying neural mechanisms were assessed by repeating baroreflex tests following cholinergic blockade with methylatropine or beta-adrenergic blockade with propranolol. Basal blood pressures always tended to be higher, while corresponding heart rates were lower, in old than in young rats. Reflex bradycardia (but not tachycardia) was initially weaker in 24-month-old rats as were reductions in both reflex bradycardia and tachycardia after cholinergic blockade. On the other hand, the reduction in reflex tachycardia following beta-adrenergic blockade in old rats was more pronounced and almost equal to that produced by combined cholinergic and beta-adrenergic blockade. From these results we conclude that with old age in male Sprague-Dawley rats, just as has been shown previously in Fischer 344 rats, predominant efferent pathways for regulating heart rate reflexes are also altered to become almost exclusively beta-adrenergic or sympathetic.

Aging↗

Mediation of reflex tachycardia becomes exclusively beta-adrenergic in old Fischer 344 rats.

To study how baroreflex regulation changes with age we compared reflex heart rate responses elicited in awake Fischer 344 rats of different ages during intravenous infusions of phenylephrine or sodium nitroprusside. Underlying neural mechanisms were assessed by repeating baroreflex tests following cholinergic blockade with methylatropine or beta-adrenergic blockade with propranolol. Basal heart rates always tended to be lower in old than in young rats, but the differences became statistically significant only after beta-adrenergic or combined cholinergic and beta-adrenergic blockade. Most reflex heart rate responses (i.e. except reflex tachycardia in males during depressor responses to sodium nitroprusside) were initially weaker in old than in younger rats. Reflex bradycardia and tachycardia were reduced equally in both age groups after cholinergic blockade, but were reduced more in old than in young rats after beta-adrenergic blockade. beta-adrenergic blockade alone reduced reflex tachycardia as much as did combined blockade thereby suggesting that the predominant neural mechanism was beta-adrenergic. Taken altogether these results are compatible with the interpretation that efferent pathways for mediating heart rate reflexes in Fischer 344 rats are altered with age such that as parasympathetic mediation diminishes, residual mediation particularly of reflex tachycardia, becomes almost exclusively beta-adrenergic or sympathetic.

Aging↗

Characterization of intracellular amyloid fibrils in the human choroid plexus epithelial cells.

Intracellular inclusions with staining properties of amyloid are very common in the aging choroid plexus epithelial cells. In many ways these inclusions show similarities with the neurofibrillary tangles, found in cerebral cortical neurons in patients with Alzheimer's dementia. We have now designed a purification method for choroid plexus amyloid and performed a transmission and scanning electron microscopic study. This shows that one form of choroid plexus inclusions, the Biondi ring, is a homogeneous globule covered with a thin layer of amyloid fibrils. Partial immunochemical characterization of the choroid plexus amyloid reveals that it is different from the neurofibrillary tangles although there are similarities.

Aged↗

Maps of receptor binding parameters in the human brain--a kinetic analysis of PET measurements.

A kinetic method is described for the estimation of neuroreceptor density as well as the rate constants for association and dissociation of rapidly equilibrating radioligands. The method is exemplified by positron emission tomographic measurements of the human brain using 11C-raclopride, a D 2 dopamine receptor antagonist, and 11C-Ro 15-1788, a benzodiazepine receptor antagonist. Using a linear non iterative algorithm, regional binding characteristics were calculated and displayed pixel by pixel in brain maps. Data from repeated experiments on the same subject with different amounts of the unlabeled ligand were utilized. The binding characteristics were determined according to a two step procedure in which the time course of the free radioligand concentration was estimated from a reference region considered to be free of specific receptor binding sites. Alternative methods to determine the concentration of free radioligand are discussed.

Algorithms↗

Morbidity after temporomandibular joint arthrography is lower than after removal of lower third molars.

The morbidity after temporomandibular joint arthrography was studied as the amount of pain, use of pain medicine, and disturbed sleep and was compared with the morbidity after removal of lower third molars. The morbidity was substantially higher after surgery than after arthrography. It was concluded that the morbidity after arthrography can be kept at a low level and that it should not restrict the indications for this examination.

Adult↗