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M Lindgren

Publications and source records attributed to M Lindgren.

At least 55 records · Page 3Linked to original sources
PubMed1995

Characterization of a folding intermediate of human carbonic anhydrase II: probing local mobility by electron paramagnetic resonance.

The spin-labeling method was used to investigate human carbonic anhydrase, HCA II, undergoing unfolding induced by guanidine-HCI (Gu-HCI). The spin-probe, N-(2,2,5,5-tetramethyl-1-yloxypyrrolidinyl-3-yl)iodoacetamide, was attached covalently to the single cysteine (position 206) in the enzyme. The electron paramagnetic resonance spectrum of the folded structure showed the characteristic slow motional spectra. When the concentration of the denaturing agent, Gu-HCI, was gradually increased, new spectral components with narrower lines evolved to give complex electron paramagnetic resonance spectra, apparently containing superimposed contributions from several components of different mobility. By a differentiation technique, it was possible to follow the relative increase of the narrow components as a function of Gu-HCI concentration. The amplitude of difference spectra versus Gu-HCI concentration showed two distinct maxima, indicating the existence of a folding intermediate state/structure. The results were found to agree with optical absorption data, which showed similar transitions at the same Gu-HCI concentrations. From line-shape simulations assuming a Brownian diffusion model, the rotational diffusion constants for the spin-label in the folded, folding intermediate, and unfolded structures were determined. The relative abundances of the three conformations in the region 0-4 M Gu-HCI were obtained by least squares fitting of the simulated spectra to the experimental ones. The folding intermediate was found to have a maximum population of 39 +/- 4% at approximately 0.7 M Gu-HCI.

Carbonic Anhydrases↗
PubMed1994

Electron paramagnetic resonance of X-irradiated sodium and potassium salts of glucose-1-phosphate. Identification of PO3(2-) radicals at room temperature.

Single crystals of the disodium and dipotassium salt of glucose-1-phosphate, X-irradiated at 80 K or at 280 K, show the presence of PO3(2-) radicals at 295 K, formed by scission of the phosphate-ester bond at the phosphate side. The 31P hyperfine coupling constants were measured using X- and Q-band EPR spectroscopy. Typical values for these coupling constants are a magnitude of = 68 mT and a perpendicular = 53 mT. The g values were almost isotropic, slightly smaller than that of the free electron spin (g = 2.0023). There is no substantial reorientation of the phosphate group in the crystalline lattice upon radical formation. Directly after irradiation at 77 K the PO3(2-) radicals are not present, but their characteristic resonance grows in upon thermal annealing of the crystals. The radicals are probably formed from a carbon-centered radical precursor by secondary reactions resulting in the loss of the phosphate group, leaving a (diamagnetic) modified carbohydrate molecule behind. The alternative process of reductive cleavage of the phosphate-ester bond by electrons released from traps in the crystal upon thermal annealing is considered less likely. A second phosphate-centered species, with a magnitude of about 21 mT and a perpendicular about 15 mT, was detected in the dipotassium salt of glucose-1-phosphate only. Possible structures for this species are discussed.

Electron Spin Resonance Spectroscopy↗
PubMed1993

Influence of prophylactic anticonvulsant therapy on high-dose busulphan kinetics.

The pharmacokinetics of high-dose busulphan was studied in 17 patients during conditioning prior to bone marrow transplantation using deuterium-labeled busulphan (d8-BU). About 50% of busulphan doses 1 and 16 was replaced with d8-BU. Patients were treated with phenytoin or diazepam as prophylactic anticonvulsant therapy. Patients who received phenytoin demonstrated significantly higher clearance (mean +/- SD, 3.32 +/- 0.99 ml min-1 kg-1), a lower area under the concentration-time curve (AUC, 5,412 +/- 1,534 ng h ml-1; corrected for dose/kilogram) and a shorter elimination half-life (3.03 +/- 0.57 h) for the last dose of d8-BU (dose 16) as compared with the first dose (2.80 +/- 0.78 ml min-1 kg-1, 6,475 +/- 2,223 ng h ml-1 and 3.94 +/- 1.10 h, respectively). No difference in the above mentioned pharmacokinetic parameters was seen in patients treated with diazepam. Moreover, a continuous decrease in the steady-state level of busulphan was observed in four of seven patients in the phenytoin-treated group, whereas in the diazepam group, such a decrease was seen in only one of eight patients. We conclude that phenytoin used as prophylactic anticonvulsant therapy alters busulphan pharmacokinetics and, most probably, its pharmacodynamics. For adequate prophylactic therapy, anticonvulsants with fewer enzyme-inductive properties than phenytoin should be used.

Adult↗
PubMed1992

[A pilot study: neuropsychological rehabilitation of patients with solvent-induced toxic encephalopathy].

Fourteen patients with chronic toxic encephalopathy underwent a neuropsychological intervention comprising crisis therapy, information about the disease, and cognitive training. Evaluation showed the patients to have experienced substantial improvement in their daily life and family relations as a result of the intervention. Their affective symptoms decreased and their verbal memory improved. Regional cerebral blood flow (rCBF) measurements showed training-dependent changes of functional activity related to change in memory strategy. This rCBF change had disappeared six months later, however, suggesting that the duration of intervention needs to be extended in order for use of the learned memory techniques to become automatic. We conclude that neuropsychological rehabilitation is effective and should be made available to patients with chronic toxic encephalopathy.

Adult↗
PubMed1992

Neuropsychological performance differs between type 1 diabetic and normal men during insulin-induced hypoglycaemia.

Cerebral function was measured with a neuropsychological test battery before, during, and after insulin-induced hypoglycaemia (blood glucose approximately 2.0 mmol l-1) in 10 male Type 1 diabetic patients (age 20-43 years, duration of diabetes 14 (2-30) years) and in 12 normal men. There were no group differences in neuropsychological results at normal glucose levels. Significant effects of hypoglycaemia were found in reaction-time measures (p less than 0.001) and in other tests requiring speed and attention (p less than 0.001), in verbal fluency (p less than 0.05), and short-term memory (p less than 0.001). Significant group effects and interactions (p less than 0.05) revealed that the diabetic patients were generally more affected by hypoglycaemia than the normal subjects. This might have been partly due to the larger absolute decrease in blood glucose level in the diabetic patients, although the rate of glucose decrease was not related to performance in either group. Thus, the diabetic brain might be more vulnerable to hypoglycaemia, perhaps through the persistent impact of repeated hypoglycaemic episodes, although no neuropsychological deficit is demonstrable at normal blood glucose levels.

Blood Glucose↗
PubMed1991

Sensation of effort and duration of mentally executed actions.

The aim of this study was to examine whether a sensation of effort would arise in subjects requested, by verbal instructions, to mentally perform motor tasks with an internal imagery strategy. Sixteen subjects had to imagine themselves, from a first person perspective, writing a sentence and drawing a Necker's cube either with their right dominant hand or with their left hand, as well as hopping around a square either on their right or left foot. The time needed to mentally execute these actions was measured. The sensation of effort following the mental performance and the difficulty of imaging the tasks were assessed by means of two analog rating scales. The results indicate that the sensation of effort increased across the trials. Furthermore, a negative correlation coefficient (mean r = -0.99) was found between the difficulty to imagining a given motor task and the subjective sensation of effort across the trials. Moreover, the sensation of effort was more pronounced when the tasks involved the non-dominant limb.

Adult↗
PubMed1991

Electron trapping and reactions in rhamnose by ESR and ENDOR.

The main objective for a reinvestigation of rhamnose was to devise a mechanistic link between the trapped electron detected previously and the secondary radicals observed at 77 K and at room temperature. Single crystals of rhamnose were X-irradiated at temperatures between 15 and 300 K and examined using ESR, ENDOR, and field-swept ENDOR techniques. After low-temperature irradiation a C3 H-abstraction radical is formed following the visible light-induced decay of the trapped electron. This species was previously assigned erroneously to a C2 H-abstraction species. At temperatures above 120 K, this radical deprotonates at the C3 hydroxy group. Furthermore, a C2 H-abstraction radical is formed following the thermally induced decay of the trapped electron. The C2 and C3 H-abstraction radicals did not convert into each other. A third radical species formed at low temperatures is a C5 H-abstraction radical. It is unstable above 250 K and decays without any apparent successor. The C2 and C3 H-abstraction radicals are formed thermally and photochemically from the parent trapped electron. The conversions are mediated by hydrogen atoms formed intermediately or by elimination of hydride ions. The thermal decomposition pathway requires further studies, in particular with respect to the possible role of water. Recently, Box et al. analyzed the site of the trapped electron in rhamnose crystals. The present results support the results obtained by these authors (Radiat. Res. 121, 262 (1990)). In particular, trapped electron vs proton distances closely match the conversion mechanisms suggested.

Electron Spin Resonance Spectroscopy↗
PubMed1990

Neurophysiological changes during insulin-induced hypoglycaemia and in the recovery period following glucose infusion in type 1 (insulin-dependent) diabetes mellitus and in normal man.

Hypoglycaemia (median venous blood glucose 1.8 mmol/l; range 1.6-2.3) was induced by an intravenous infusion of regular insulin in eight patients with Type 1 (insulin-dependent) diabetes mellitus (age 28.0 +/- 7.4 years; mean +/- SD, duration 15.5 +/- 5.1 years) and in 12 age-matched healthy male control subjects. Multi-channel frequency analysis of electroencephalogram (electrophysiologic brain mapping) and recording of P300 and somatosensory evoked potentials were performed before, during and immediately after the hypoglycaemic period. The hypoglycaemia produced a significant increase in low frequency electroencephalographic activity in both groups, most pronounced over anterior regions of the brain. The electroencephalographic activity was normalised immediately after the hypoglycaemic period. The patients with diabetes showed somewhat longer P300 latencies during the initial normoglycaemic examination. Hypoglycaemia caused a marked reduction of the P300 amplitude in both groups of subjects and the amplitude was not restored immediately after normalisation of blood glucose levels. The somatosensory cortical responses were not affected by hypoglycaemia. We conclude that hypoglycaemia results in impairment in cerebral function, as measured by neurophysiological techniques, which is not immediately normalised when blood glucose is restored to normal.

Adult↗
PubMed1989

Regional cerebral blood flow at the time of diagnosis of chronic toxic encephalopathy induced by organic-solvent exposure and after the cessation of exposure.

Regional cerebral blood flow was measured in patients with the diagnosis of chronic toxic encephalopathy induced by exposure to organic solvents. Measurements were made at the time of diagnosis and 24-84 months after the cessation of exposure. During the follow-up the patients were carefully examined for other possible causes of brain dysfunction. Comparisons were made to unexposed and solvent-exposed referents. At the first examination the patients had a 7% lower mean flow level than the unexposed referents and a 5% lower level than the exposed workers. The largest flow differences were seen in the frontotemporal areas. At the follow-up, the difference in the mean flow level between the patients and referents was no longer significant. Regionally, the flow had increased, especially in areas which initially showed the most pronounced decreases. There was a significant negative correlation between the initial cerebral blood flow level and the degree of normalization of the flow level at follow-up.

Adult↗
PubMed1988

Prospective clinical and psychometric investigation of patients with chronic toxic encephalopathy induced by solvents.

Sixty-two patients with chronic toxic encephalopathy diagnosed in 1976-1981 were considered for reexamination in 1983-1984. Thirteen were found to have other diseases that might contribute to brain dysfunction. Seventeen were unwilling or unable to participate. The final group consisted of 32 men 33 to 63 (median 55) years of age who were physically and psychometrically reexamined with the same methods used in the initial investigation. The interval between the first and present examination was 21-88 (median 48) months, and exposure to solvents had ceased. The subjects reported some improvement in their neurasthenic problems. In particular they suffered less from fatigue, headache, and dizziness. When diagnosed they had an average of seven out of ten typical neurasthenic symptoms included in the toxic encephalopathy syndrome. At the time of the follow-up the mean number of symptoms had decreased significantly to five. The psychometric retesting showed significant deterioration in verbal memory, improvement in visual memory, and unchanged results on the other tests. In conclusion, these toxic encephalopathy patients improved subjectively when exposure stopped. Psychometrically they performed very close to the initial testing, which excluded progressive brain disease or subacute pharmacological solvent intoxication.

Adult↗
PubMed1987

Computed tomography and psychometric test performances in patients with solvent induced chronic toxic encephalopathy and healthy controls.

Patients with chronic toxic encephalopathy caused by occupational exposure to organic solvents and diagnosed between 1976 and 1981 have been re-examined during a follow up period of 21-88 months (median 48). Thirty two patients underwent computed brain tomography (CT), were retested psychometrically, and the results were compared with a group of age matched control subjects from the same socioeconomic level. The age of the patients was 33-69 (median 55) and they had been exposed to organic solvents for 7-50 years (median 26). The CT examinations were quantified by linear measurements on the films of the four largest sulci, the minimum width of the cella media and the third ventricle. Bifrontal horn, bicaudate, and third ventricle--Sylvian fissure distances were also measured; and measurements were adjusted for variation in skull diameter. No differences were found between the patients and controls. Most of the measures were correlated with age, to a somewhat higher degree in the patients. The patient-control differences did not increase with increasing age of the subjects. Psychometrically the patients performed worse than the controls despite adjustments for possible differences of intellectual level in the two groups. In the patients correlations were found between some of the CT measures and psychometric test performances suggesting slower psychomotor speed and attention difficulties among subjects with central and cortical brain substance reduction. No such correlation was found in the control group. It is concluded that patients with solvent induced chronic toxic encephalopathy have no severe loss of brain substance.

Adult↗
PubMed1981

Combined modality therapy of operated astrocytomas grade III and IV. Confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time: a prospective multicenter trial of the Scandinavian Glioblastoma Study Group.

In a controlled, prospective, randomized investigation, started in 1974, 118 patients with supratentorial astrocytoma Grade III--IV were divided into three groups. Groups 1 and 2 received 45 Gy postoperatively to the whole supratentorial brain. Bleomycin in 15-mg doses and a total dose of 180 mg or placebo was given intravenously three times a week, one hour prior to radiotherapy, during weeks 1, 2, 4 and 5. Group 3 received conventional care but no radiotherapy or chemotherapy. Median survival rates of patients were 10.8 months in Groups 1 and 2, and 5.2 months in Groups 3, a statistically significant difference. With regard to performance, the patients in Group 3 deteriorated faster than patients in Groups 1 and 2. Bleomycin had no positive or negative influence on survival.

Adult↗