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Biomedical subjects

T Andersson

Publications and source records attributed to T Andersson.

At least 109 records · Page 6Linked to original sources
PubMed1995

Biochemical and physiological effects in fish exposed to bleached kraft mill effluents.

The studies were performed on perch (Perca fluviatilis) caught outside Husum and Iggesund kraft pulp mills in 1985 and 1987, respectively, and the results were compared to previous observations from 1984 to 1985 in the receiving waters of the Norrsundet kraft pulp mill. The studies revealed that the biochemical and physiological variables, i.e., EROD activity, gonad size, number of lymphocytes, carbohydrate metabolites, and plasma ion composition, can be used as sensitive and reliable indicators of toxic effects on natural populations of fish exposed to conventional chlorine-bleached kraft mill effluents. However; the effects were generally less pronounced and indicated less geographic extension than those seen in perch previously investigated in the receiving waters of the Norrsundet kraft pulp mill. Based on these studies on perch at Husum and Iggesund and the previous studies at Norrsundet it can be concluded that the chlorine-bleached kraft mill effluents cause serious disturbances to vital biochemical and physiological functions, which can affect the health status and presumably also the survival of the fish. Finally, the responses do not reflect the present situation in the receiving waters since all three mills have taken extensive measures for process alterations and discharge reductions after the time of the investigations.

Animals↗
PubMed1995

The Ca2+ signaling capacity of the beta 2-integrin on HL60-granulocytic cells is abrogated following phosphorylation of its CD18-chain: relation to impaired protein tyrosine phosphorylation.

The phosphorylation state of the CD18-chain of beta 2-integrins have been shown not to mediate changes in the avidity of these receptors (i.e., inside-out signaling); however, no alternative functional significance has been proposed. Our study focused on how changes in the phosphorylation state of beta 2-integrin-receptors on HL60-granulocytic cells are related to its intracellular signal transduction properties (i.e., outside-in signaling). Engagement of beta 2-integrins on differentiated HL60 cells induced a transient increase in the cytosolic free Ca2+ concentration and an increased tyrosine phosphorylation of three major protein bands (70, 115, and 140 kDa). These signaling events occurred without any detectable phosphorylation of the CD18-chain. However, a strong phosphorylation of the CD18-chain by preexposure to phorbol myristate acetate (PMA) coincided with an abolishment of both the beta 2-integrin-induced Ca2+ signal and the protein tyrosine phosphorylations. By comparison, none of these effects were exhibited by 4-alpha-PMA, an analogue that does not activate protein kinase C. Thus, phosphorylation of the CD18-chain of beta 2-integrins is not required for outside-in signal transduction by these receptors, but it could constitute an effective mechanism by which the signaling properties of beta 2-integrins can be modulated by exogenous factors and possibly also by intracellular signals induced by other receptors. The fact that both the cytosolic free Ca2+ signal and protein tyrosine phosphorylations were abrogated by PMA suggests an intimate relationship between these two intracellular signals. To explore this possible relationship, we chelated the beta 2-integrin-induced Ca2+ signal with BAPTA. The beta 2-integrin-induced protein tyrosine phosphorylations were blocked by BAPTA but not by abolishment of the Ca2+ signal due to chelation with MAPT or by pretreatment with thapsigargin. These findings and the observation that pretreatment of cells with methyl-2,5-dihydroxycinnamate (a tyrosine kinase inhibitor) blocked the beta 2-integrin- but not the fMet-Leu-Phe-induced Ca2+ signal suggest that beta 2-integrin-induced tyrosine kinase activation occurs prior to and is a prerequisite for the subsequent Ca2+ signal.

CD18 Antigens↗
PubMed1995

Chemoattractant-induced NADPH oxidase activity in human monocytes is terminated without any association of receptor-ligand complex to cytoskeleton.

When the chemotactic peptide formylmethionyl-leucyl-phenylalanine binds to its cell surface receptor, a transmembrane signal is generated that activates the superoxide-producing NADPH oxidase of human phagocytes. Comparing monocytes and neutrophils with regard to the production of superoxide anion induced by the peptide, we found a similar time-course for both types of cells. In neutrophils, ligand binding induced a conversion of the receptor to a high-affinity form, a change suggested to be due to an association of the receptor-ligand complex to the Triton X-100-insoluble cytoskeleton. This event has been hypothesized to terminate the signal that activates the NADPH oxidase and thereby results in cessation of the cellular production of superoxide anion. Neutrophils preincubated with the cytoskeleton-disrupting drug cytochalasin B showed an increased and prolonged superoxide anion production after activation with the peptide, thus indicating that the cytoskeleton is involved in terminating this response. Formylmethionyl-leucyl-phenylalanine was also found to induce polymerization of actin in monocytes; however, cytochalasin B had no effect on the peptide-induced generation of superoxide anion in these cells. Furthermore, also in monocytes, ligand binding induced a conversion of the receptor to a high-affinity form; however, the receptor-ligand complex did not coisolate with the Triton X-100-insoluble cytoskeleton. These results indicate that, in monocytes, the NADPH oxidase activating pathway is terminated without any association of the receptor-ligand complex to the Triton X-100-insoluble cytoskeleton.

Actins↗
PubMed1995

Eye symptoms, visual evoked potentials and EEG during intravenous infusion of glycine.

Disturbance of vision is a complication that may occur from absorption of the glycine solution used to irrigate the bladder during transurethral operations. We examined for a possible dose-response relationship between glycine dose, eye symptoms and neurophysiological changes after repeated intermittent intravenous infusions of 4.4 g of glycine for up to 22 g over 1 h in 10 male volunteers. The serum glycine concentration increased from 230 +/- 75 to 5,232 +/- 1,088 mumol/l (mean +/- s.d.) during the infusions. We found an increase in diastolic arterial pressure but no significant changes in systolic pressure, heart rate or mental status. Five of the volunteers developed blurring of vision which lasted for 10-30 min. The visual evoked potentials (VEP) of these subjects showed an increase of the P100 and N70 latencies which started after no more than 4.4 g of glycine had been administered. The amplitude of the VEP was preserved and the main frequency of the EEG did not change, indicating that VEP changes were not due to cortical dysfunction. There was no dose-response relationship between glycine infusion and eye symptoms but a sub-group of volunteers responded with both visual disturbances and VEP changes.

Adult↗
PubMed1995

Ventilation-perfusion inequality in nocturnal hypoxaemia due to chronic obstructive lung disease (COLD).

Nocturnal hypoxaemia is often noted in COLD patients with a daytime PaO2 above 8.0 kPa. It has been assumed that ventilation-perfusion inequality contributes to nocturnal hypoxaemia. 10 patients with advanced COLD [median FEV1 0.73 (range 0.50-1.32)l], but without daytime hypoxaemia [median PaO2 8.35 (range 8.0-12.2) kPa] were investigated with regard to possible nocturnal hypoxaemia using polysomnography. Daytime lung function was assessed by spirometry and carbon monoxide diffusion capacity (DLCO). Daytime ventilation-perfusion (VA/Q) relationships were measured by the multiple inert gas elimination technique. Dispersion of perfusion and ventilation distributions was increased [log SDQ 1.01 (range 0.80-1.35) and log SDV 0.91 (range 0.69-1.86) resp.]. Around 8% of the ventilation was directed towards high VA/Q areas (10 < VA/Q < 100). All subjects reached all sleep stages, and all but one had a nadir nocturnal oxygen saturation (SaO2) of below 90%. Their median lowest nocturnal SaO2 was 84.0 (range 70-93)% and their mean oxygen saturation in the course of desaturation episodes (MminSaO2) was 86.4 (range 83.6-91.5)%. An increased mean VA/Q ratio of ventilation distribution was associated with a reduced DLCO. Increased nocturnal episodes of wakefulness and of stage I sleep correlated with increased dead space ventilation and dispersion of the ventilation distribution. Patients with deep nocturnal desaturations had a low mean VA/Q ratio of the perfusion distribution (Q mean) (r = 0.87, P < 0.01) and increased perfusion of inferior VA/Q areas (0.1 VA/Q < 0.3). Low MminSaO2 was associated with low morning PaO2 and a low Q mean. COLD patient with solely nocturnal hypoxaemia have a high degree of pulmonary hyperinflation and emphysema. Increased sleep disruption is associated with more severe small airway disease. Increased perfusion of sparsely ventilated areas is associated with more pronounced nocturnal desaturations.

Aged↗
PubMed1995

Human in vivo cutaneous microdialysis: estimation of histamine release in cold urticaria.

A novel bioanalytical in vivo sampling technique, cutaneous microdialysis, was used to follow the chronology of skin histamine release in 3 patients with cold urticaria and in 2 healthy volunteers. Laser Doppler perfusion imaging was used simultaneously to monitor the skin circulatory response. Microdialysis samples were collected at 10-min intervals and analysed by radioimmunoassay technique. Fifty minutes after probe insertion, the ventral forearm skin in the area of the dialysis membrane was provoked for 5-15 min with a 25 x 40 mm ice cube covered with plastic foil. In the cold urticaria patients, an up to 80-fold increase of histamine was observed, with peak levels 20-30 min after challenge. Histamine levels then fell to reach "baseline" levels within 50 min. In the healthy subjects, the histamine increase was earlier, less pronounced and of shorter duration. Cutaneous microdialysis and laser Doppler imaging offer new possibilities for the chronological multiparameter assessment of inflammatory skin disorders in vivo.

Adult↗
PubMed1995

An analysis of VEP components in optic neuritis.

Various VEP parameters were analysed in 126 patients with multiple sclerosis, isolated optic neuritis or isolated myelopathy. The single most common deviation in eyes with clinical evidence of optic neuritis was a prolongation of the latency to P100. After the findings concerning P100 and N70 were combined two patterns of abnormalities emerged: 1) delayed P100 and delayed N70, 2) delayed P100 and absence of N70. In a few cases only one of the potentials was affected. Also in eyes without clinical evidence of optic neuritis the same patterns occurred but discrepancies between N70 and P100 were more common, especially the combination of normal P100 and delayed or absent N70. In about half of these cases the latency to P100 was close to the upper normal limit. It is concluded that in such cases the additional findings of an absent or delayed N70 is strongly suggestive of visual system dysfunction and that the inclusion of N70 in the analysis of VEP may increase the diagnostic yield of the examination.

Adult↗
PubMed1994

Caffeine metabolism by human hepatic cytochromes P450: contributions of 1A2, 2E1 and 3A isoforms.

Caffeine (CA) N1-, N3- and N7-demethylase, CA 8-hydroxylase and phenacetin O-deethylase activities were measured in microsomes from 18 separate human livers which had been characterized previously for a range of cytochrome P450 (CYP) isoform-specific activities and immunoreactive CYP protein contents. Correlations between the high affinity components of the three separate CA N-demethylations were highly significant (r = 0.77-0.91, P < 0.001) and each of the three high affinity CA N-demethylations correlated significantly (r = 0.64-0.93, P < 0.05-0.001) with the high affinity phenacetin O-deethylase, 2-acetylaminofluorene N-hydroxylation and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) mutagenicity (all predominantly CYP1A2-mediated reactions). Consistent with these observations, cDNA-expressed human CYP1A2 catalyzed the N1-, N3- and N7-demethylation of CA and apparent Km values were similar (0.24-0.28 mM) for all three reactions and comparable to those observed previously with human liver microsomes. The low affinity components of CA N1- and N7-demethylation correlated significantly (r = 0.55-0.85, P < 0.05-0.001) with immunoreactive CYP2E1 content and the CYP2E1-specific activities 4-nitrophenol and chlorzoxazone hydroxylation. Diethyldithiocarbamate, a selective inhibitor of CYP2E1, inhibited the low affinity CA N1- and N7-demethylation, with IC50 values of 23 microM and 11 microM, respectively. The apparent Km values for CA N1- and N7-demethylation by cDNA-expressed CYP2E1 (namely 28 and 43 mM, respectively) were of a similar order to those calculated for the low affinity microsomal activities. Significant correlations (r = 0.87-0.97, P < 0.001) were observed between CA 8-hydroxylation and immunoreactive CYP3A content and the CYP3A-mediated reactions benzo(a)pyrene hydroxylation, omeprazole sulfoxidation and aflatoxin B1 mutagenesis. Effects of alpha-naphthoflavone, erythromycin, troleandomycin and nifedipine on microsomal CA 8-hydroxylation were generally consistent with CYP3A involvement. Taken together with previous data, the results indicate a major involvement of CYP1A2 in the high affinity component of all three human hepatic CA N-demethylations. In contrast, CYP2E1 appears to be the main enzyme involved in the low affinity components of CA N1- and N7-demethylation while CA 8-hydroxylation is catalysed predominantly by a CYP3A isoform(s).

Caffeine↗
PubMed1994

Chemotactic factor receptor activation transiently impairs the Ca2+ signaling capacity of beta 2 integrins on human neutrophils.

Neutrophil motility involves a delicate interplay between intracellular signals elicited by adhesion and chemotactic factor receptors. To explore certain aspects of these complex receptor interactions in neutrophils, we studied how engagement of the chemotactic receptor for N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe) and the beta 2 integrins affect the Ca2+ signaling properties of each other. Specific antibody engagement of the beta 2 integrins on suspended neutrophils generated both an intracellular mobilization and an influx of Ca2+, effects which could be temporarily impaired by preengaging the fMet-Leu-Phe receptors on the cells. In contrast to these findings, preengagement of the beta 2 integrins on suspended neutrophils affected neither a subsequent fMet-Leu-Phe-induced mobilization of Ca2+ nor an influx of Ca2+ from outside the cell. We also found that fMet-Leu-Phe could mobilize intracellular Ca2+ after a premobilization of Ca2+ via beta 2 integrins, despite the fact that both receptors mobilize Ca2+ from thapsigargin-sensitive intracellular stores. The findings that preactivation of beta 2 integrins did not affect the ability of fMet-Leu-Phe to induce an intracellular Ca2+ signal, whereas preactivation of fMet-Leu-Phe receptors transiently impaired the Ca2+ signaling ability of beta 2 integrins, suggest that the fMet-Leu-Phe-induced reduction is due to an interaction upstream of the release of Ca2+ from intracellular stores.

Antibodies, Monoclonal↗
PubMed1994

Comparison of visual evoked potentials elicited by light-emitting diodes and TV monitor stimulation in patients with multiple sclerosis and potentially related conditions.

Visual evoked potentials elicited by reversal of a checkerboard pattern constructed of square, red light-emitting diodes (LEDs) were compared with a conventional black and white pattern displayed on a TV monitor in control subjects and in 71 patients with established or suspected multiple sclerosis. Both stimuli elicited distinct responses in the control groups: the latencies were longer with LED stimulation while the amplitudes of the various components were differently altered. The frequency of abnormal responses among the patients was higher with LED stimulation than with TV stimulation, but the highest diagnostic yield was obtained when both methods were combined.

Adolescent↗
PubMed1994

Phrenic nerve stimulation during halothane anesthesia. Effects of atelectasis.

BACKGROUND: Atelectasis formation during anesthesia may be due to loss of respiratory muscle tone, in particular that of the diaphragm. This was tested by tensing the diaphragm by phrenic nerve stimulation (PNS) and observing the effect on atelectasis. METHODS: Twelve patients (mean age 48 yr) without preexisting lung disease were studied during halothane anesthesia. PNS was executed with an external electrode on the right side of the neck. Chest dimensions and area of atelectasis were studied by computed tomography of the chest. RESULTS: Right-sided PNS against an occluded airway at functional residual capacity reduced the atelectatic area in the right lung from 5.1 to 3.8 cm2. The atelectasis was reduced to 1.1 cm2 after application of positive end-expiratory pressure (PEEP) of 10 cmH2O and large tidal volumes but increased to 2.5 cm2 within 1 min after discontinuation of PEEP. Commencement of PNS immediately after PEEP prevented the atelectasis from increasing, the mean area being 0.9 cm2. In seven patients, in whom the trachea was intubated with a double-lumen endobronchial catheter the atelectatic area was smaller during PNS with an open airway than during positive pressure inflation of the lung with the same volume as inspired during PNS (3.5 and 5.2 cm2, respectively. CONCLUSIONS: The findings indicate that contracting the diaphragm in the anesthetized subject reduces the size of atelectasis.

Adult↗
PubMed1994

Interethnic differences in omeprazole metabolism in the two S-mephenytoin hydroxylation phenotypes studied in Caucasians and Orientals.

Two independent studies showed that the 5-hydroxylation, but not the sulfoxidation, of omeprazole is more rapid in extensive metabolizers (EMs) than in poor metabolizers (PMs) of S-mephenytoin. In Caucasian, Chinese, and Korean PMs, the mean oral clearances were similar and not significantly different (85, 73, and 59 ml h-1 kg-1, respectively). However, the geometric mean clearance in Caucasian EMs (950 ml h-1 kg-1) was higher than in both Chinese EMs (426 ml h-1 kg-1, p < 0.05) and Korean EMs (446 ml h-1 kg-1, p < 0.01). The incidence of PMs of S-mephenytoin is higher in Chinese (14.6%) and Koreans (12.6%) than in Swedish Caucasians (3.3%). Therefore, the proportion of heterozygous compared to homozygous EMs is higher in Orientals than in Caucasians. This might explain the higher clearance of omeprazole in Caucasian EMs compared to the clearance of omeprazole in Chinese and Korean EMs of S-mephenytoin.

Aryl Hydrocarbon Hydroxylases↗
PubMed1994

Changes in skin circulation after insertion of a microdialysis probe visualized by laser Doppler perfusion imaging.

Microdialysis makes possible in vivo estimation of endogenous and exogenous substances in the dermal extracellular space. Insertion of the microdialysis probe and its subsequent presence in the skin may affect both the reactivity of the skin test site and the measurement of target substances. Laser Doppler flowmetry is a non-invasive method for estimating cutaneous blood flow. A further development of this technique, laser Doppler perfusion imaging, has been used to study the time course of the circulatory changes caused in the area of microdialysis probe insertion. Laser Doppler perfusion imaging was performed prior to, during, and after microdialysis probe insertion in the skin of the ventral forearm in three subjects. Probe insertion caused an increase in skin blood perfusion in the whole test area. About 15 min after probe insertion, the flare, which is presumed to be of chiefly axon reflex origin, began to subside and the circulatory response could be seen to center around the site of insertion and the tip of the probe. Skin perfusion levels had returned to near normal levels within 60 min. Local anesthesia of the point of guide insertion inhibited the flare, but did not affect circulatory reactivity in the skin nearby. Both microdialysis and laser Doppler perfusion imaging seem to be promising new methods in dermatologic research.

Adult↗