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Biomedical subjects

O Eriksson

Publications and source records attributed to O Eriksson.

At least 19 recordsLinked to original sources

Inhibition of lipid peroxidation in isolated rat liver mitochondria by the general anaesthetic propofol.

The effect of the general anaesthetic propofol (2,6-diisopropylphenol) on lipid peroxidation in rat liver mitochondria was assessed with the thiobarbituric acid (TBA) assay. Propofol was shown to inhibit the accumulation of TBA-reactive compounds after initiation of radical production by the addition of the ADP-Fe2+ complex. Analysis of kinetics showed that propofol caused a concentration-dependent delay as well as a decrease in the rate of the peroxidation process. 1H-NMR spectra of mitochondrial lipid extracts indicated that 95% of the added propofol remained intact after 30 min incubation under conditions of low oxidative stress. The ESR spectrum of propofol incubated in the presence of EDTA-Fe2+ and H2O2 as initiators of radical production showed a radical that was most likely a decomposition product of the primary phenoxy radical of propofol. It is concluded that (a) propofol acts as a chain reaction-breaking antioxidant by forming a stable radical and (b) propofol does not seem to be metabolized in mitochondria in vitro.

Adenosine Diphosphate

The role of endotoxins in induced ruminal acidosis in calves.

Experimentally induced ruminal acidosis was carried out in 4 calves to investigate the possibility of resorption of endotoxins from Gram negative bacteria originating from the gastro-intestinal tract. The ruminal acidosis was induced by overfeeding of oats and the effect was evaluated by clinical and blood biochemical changes. Blood samples were collected every 2 h for 60 h before and after experimental feeding. The animals showed signs of ruminal acidosis and also the clinical and blood biochemical changes were similar to those seen after experimental endotoxaemia. However, although being less dramatic the changes in many relevant parameters such as an increase in prostaglandin F metabolite levels, body temperature, endotoxins and a decrease in iron indicate that an endotoxaemic state had occurred. The results of the present study show that ruminal acidosis/stasis is linked to resorption of endotoxins from the gastro-intestinal tract causing endotoxaemia/endotoxicosis.

Acidosis

Effects of the membrane potential upon the Ca(2+)- and cumene hydroperoxide-induced permeabilization of the inner mitochondrial membrane.

A protonophore-induced delta psi decrease in a 180-140 mV range causes an increase in the lag-period of Ca(2+)-induced mitochondrial permeabilization but has little effect on the cumene hydroperoxide-induced permeability transition of mitochondria. Suppression of the non-specific permeability induction seems to be mediated by an increase in [ADP] in the mitochondrial matrix. A further decrease in delta psi leads to additional suppression of the non-specific permeability as a result of a partial ruthenium red-sensitive efflux of the previously accumulated Ca2+. On the other hand, complete dissipation of delta psi causes immediate induction of the non-specific permeability. It is concluded that only complete dissipation of delta psi caused by H+ leakages may act as a trigger for non-specific permeability induction.

Animals

1H-NMR studies of lipid extracts of rat liver mitochondria.

Lipid extracts of rat liver mitochondria were studied by 1H-NMR at 200 MHz. Each spectrum, obtained in 6 min with routine acquisition parameters, allowed the estimation of the phosphatidylcholine/phosphatidylethanolamine ratio, the cholesterol/total lipid molar ratio, the average fatty acid length, the unsaturation ratio and the oxidation state of the ubiquinone/ubiquinol couple. 1H-NMR spectroscopy was also used to analyze structural changes of the lipids following peroxidation. In model liposomes subjected to enzymatic peroxidation the appearance of hydroperoxides and conjugated double bonds were detected, whereas in mitochondria no such changes were seen even after a period of relatively high oxidative stress. This suggests that the systems for protection against oxidative damage in mitochondria are able to keep the amount of peroxidation products below the detection limit of the technique.

Animals

Effects of the general anaesthetic Propofol on the Ca2(+)-induced permeabilization of rat liver mitochondria.

The molecular mechanism of the Ca2(+)-induced permeabilization of rat liver mitochondria was evaluated by studying a new effect of the commonly used general anaesthetic Propofol (2,6-diisopropylphenol). The compound was found to induce an apparent uptake of Ca2+ at steady-state in the Ca2(+)-distribution between the medium and the mitochondria, and to inhibit swelling and release of accumulated Ca2+ induced by inorganic phosphate, t-butyl hydroperoxide, diamide or FCCP plus Ruthenium red. The compound did not stimulate the activity of the Ca2(+)-uniporter and it is concluded that the effects seen are due to the inhibition of the Ca2(+)-dependent, unspecific permeability increase. The results suggest two mechanisms whereby Propofol stabilizes the mitochondrial membrane in the presence of Ca2+: (i) by interaction with the putative pore, thus causing its closure; and (ii) by scavenging of free radicals thus inhibiting its opening during oxidative stress.

Animals

Vaginal immunoglobulin A (IgA) levels in post-menopausal women: influence of oestriol therapy.

The concentration of secretory immunoglobulin A (IgA) in the vaginal fluid of 20 untreated post-menopausal women (aged 75.4 +/- 1.4 years) was compared with the levels in a group of 20 post-menopausal women (aged 73.2 +/- 1.5 years) treated with oral oestriol (E3) (2 mg/day) and a further group of 20 healthy, non-pregnant, fertile women (aged 28.2 +/- 1.8 years). Secretory IgA was determined using a paper disc modification of the single radial immunodiffusion technique. The vaginal concentration of IgA in the untreated women was 41.5 +/- 5.7 mg/l, which was higher than that recorded in those treated with E3 (20.8 +/- 5.7 mg/l, P less than 0.05) and in the fertile women (16.4 +/- 3.7 mg/l, P less than 0.01). Epithelial cells predominated in the wet smear preparations obtained from the women who received E3 and the fertile women, while a predominance of leucocytes was observed in the untreated women. Lactobacilli were found more frequently in the vaginal flora of the women in the E3 group (P less than 0.001) and the fertile women (P less than 0.001) than the untreated group. Faecal-type bacteria were seen more frequently in the vaginal flora of the untreated women than the E3 group (P less than 0.01) or the fertile women (P less than 0.001). The possible implications of the present findings with regard to the individual variation in the intensity of symptoms experienced by women suffering from the oestrogen deficiency syndrome are discussed.

Adult

A health care program for the investigation and treatment of elderly women with urinary incontinence and related urogenital symptoms.

The assessment and treatment of urinary incontinence and related urogenital symptoms using an algorithm model was evaluated in 364 elderly women complaining of urinary incontinence. The women (age 72.1 +/- 1.5 years, range 65-84 years) were assessed by a 48-hour pad test, a cough provocation test, micturition lists and a gynecological examination which included a smear test, measurement of vaginal pH and bacterial cultures. The diagnosis of urinary incontinence was confirmed in 346 women (stress 26.3%; urge: 32.7%; mixed: 41.0%). Women suffering from stress incontinence were younger (p less than 0.05) and had experienced a larger number of deliveries (p less than 0.05) than women with urge incontinence. All the women were treated with oral estriol, 3 mg daily for 4 weeks followed by 1-2 mg daily. The total urinary leakage per 48 hours (p less than 0.01) and maximum single leakage (p less than 0.05) were reduced in women with mixed incontinence, while the frequency of micturition decreased (p less than 0.05) in women with urge incontinence after 12 weeks treatment with oral estriol. There were no significant changes in any of the objective micturition parameters in women with stress incontinence following treatment. Karyopyknotic index and the presence of lactobacilli were increased (p less than 0.001), and vaginal pH decreased (p less than 0.001) following treatment in women with all types of incontinence. More than 70% of all the women treated in this algorithm model judged themselves to be improved, much improved or cured.

Aged

Effects of vitamin A on endotoxaemia in rats.

OBJECTIVES: To find out if survival after peritonitis induced by caecal puncture and injection of endotoxin is correlated with serum endotoxin concentrations in rats; whether this study could be carried out by studying the effects of vitamin A in rats with peritonitis; and if it was possible to differentiate between local and systemic effects of vitamin A on endotoxaemia in rats. DESIGN: Prospective randomised study. MATERIAL: Sixty adult male Sprague-Dawley rats. INTERVENTIONS: Rats were kept on a diet containing no vitamin A for six days; 30 were given vitamin A 1,380 IU/kg/day intramuscularly and 30 were given peanut oil. Peritonitis was then induced in 16 rats by caecal puncture (treated n = 10, untreated n = 6) and the remainder received intraperitoneal injections of either 0.5 mg/kg endotoxin, or 2.0 mg/kg endotoxin. MAIN OUTCOME MEASURES: Plasma concentrations of vitamin A, vitamin E, and serum concentrations of endotoxin, estimation of erythrocyte volume fraction and leucocyte particle concentrations, and survival. RESULTS: Rats that were given 2 mg of endotoxin had higher mortality and did generally less well than others. Serum endotoxin concentrations were lower in those groups that had been pretreated with vitamin A. No animal developed vitamin A deficiency and there were no differences in erythrocyte volume fraction or leucocyte particle concentration between those that did and did not receive vitamin A. CONCLUSION: Vitamin A lowered the concentration of endotoxin in the circulation, it has a central function in the host's defence against endotoxin, and the experimental model seems suitable for the study of the effect of vitamin A or endotoxemia and peritonitis.

Animals

Low doses of quinine during a short time period are effective for clearance of Plasmodium falciparum in asymptomatic children in Guinea Bissau.

Asymptomatic children in Guinea Bissau were given 5 mg quinine per kg body weight two times daily for 5 days (n = 18) or 3 days (n = 20) for treatment of Plasmodium falciparum. Parasites disappeared within four days after initiation of treatment and remained absent during the first week afterwards. Six children reported adverse reactions, mainly mild tinnitus which disappeared after termination of treatment. Reduced doses of quinine for shorter treatment periods was effective in this study. Further studies in symptomatic patients are needed to elucidate whether this low-dose regimen could be an alternative to chloro-quine in the treatment of P. falciparum in Africa.

Adolescent

Quantitative determination of endotoxins on surgical gloves.

The amount of endotoxin on surgical gloves was investigated by the limulus chromogenic substrate method. Heavy endotoxin contamination was observed on the outside of certain surgical gloves sold in Sweden. Given an endotoxin absorption of 10% to the patients, one of the types of gloves studied would cause fever, chills, headache and muscle pain. The amount of endotoxin on the gloves could be minimized by rinsing in endotoxin-free water. We conclude that the manufacturing process of latex gloves should be checked microbiologically for Gram-negative bacteria before sterilization. Alternatively, the amount of endotoxin should be checked on the product by the limulus ameobocyte lysate test before release.

Endotoxins

Analysis of reproducibility of subjective grading systems for breast carcinoma.

The inter- and intra-observer reproducibility of three grading systems for breast cancer has been analysed: those of the World Health Organisation, of Black, and of Hartveit. In addition, the components forming the basis of these grading systems were analysed separately with regard to reproducibility and interrelationship. In this analysis, degree of differentiation was also included as a parameter. The grading systems of WHO and of Black gave a stratification of the material into three categories of tumours, but that of Hartveit did not. All three systems had a low inter- and intra-observer reproducibility. Truncated component analysis indicated that the grading systems of WHO and of Black are closely related to each other and to the 'nuclear lobulation' component of Hartveit's system. The components 'pleomorphism', 'mitotic frequency', and 'hyperchromasia' of the WHO system were closely interrelated. Descriptors such as 'differentiation' and 'tubule formation' were interrelated but acted in a different direction from the others.

Breast Neoplasms

High resolution segmentation of cervical cells.

A major problem in the automation of cervical cytology screening is the segmentation of cell images. This paper presents the present status of the work on that problem at the University of Uppsala. A dual resolution system is used. Suspect malignant cells are located at 4 mu resolution. Each such cell is rescanned at 0.5 mu resolution at two different wavelengths, 530 and 570 nm. The nucleus and the cytoplasm are isolated each by two independent methods. For the nucleus adaptive thresholding in the histogram of the 570 nm image and a contouring in a radially transformed version of that image is used. For the cytoplasm a two dimensional thresholding in the 2D histogram and a contouring in a radially transformed version of the 530 nm image is used. If the two nuclear masks agree the surrounding area is checked for disturbing objects. If also the cytoplasm masks agree and are without disturbing objects the whole cell is accepted. The result of the cytoplasm masks agree and are without disturbing objects the whole cell is accepted. The result of the segmentation is thus three categories; free cells, free nuclei and rejected objects. The shape of the objects belonging to the former two categories is checked and irregularly shaped ones are rejected as probably consisting of several overlapping nuclei. Cells passing also this test are classified as normal or malignant. The experience from using this algorithm is discussed and areas for further research are pointed out.

Cell Nucleus

Special considerations with regard to the dosage of tranexamic acid in patients with chronic renal diseases.

Tranexamic acid is a potent antifibrinolytic drug frequently used in the treatment of haematuria and a number of other haemorrhagic conditions. Since it is eliminated mainly in the urine, the drug accumulates in patients with uraemia. The excretion of tranexamic acid in patients with renal failure has been investigated and dosage recommendations are given for tranexamic acid therapy in cases of renal failure.

Biological Availability

A simplified radioimmunoassay for melatonin and its application to biological fluids. Preliminary observations on the half-life of plasma melatonin in man.

A simplified and rapid radioimmunoassay (RIA) for melatonin is presented. Melatonin is extracted from seru, plasma or urine and RIA is performed by using [3H]melatonin as the tracer. The standard curve covers the range 0.2--4.3 nmol/l. By increasing the sample volume the range can be extended to 0.06 nmol/l. The intra-assay variability is 7% (relative standard deviation = rsd) and the inter-assay variability is 10% (rsd). The recovery of melatonin added to calf serum is 96%. The long term variability of the assay (43 assays on aliquots of one serum sample during 6 months) is 13.5% (rsd). The serum levels in man after one oral dose of 430 mumol melatonin have been measured. The peak value, 620 nmol/l, was noted after 0.5 h and the melatonin concentration was still above the normal range at 24 h (2.1 nmol/l).

Growth Hormone

Computer analysis of cervical cells. Automatic feature extraction and classification.

A prescreening instrument for cervical smears using computerized image processing and pattern recognition techniques requires that single cells in the specimen can be automatically isolated and analyzed. This paper describes a dual wavelength method for automatic isolation of the cytoplasm and nuclei of cells. Density-oriented, shape-oriented and texture-oriented parameters were calculated and evaluated for more than 600 cells. It is shown that the computer can be taught to distinguish between normal and atypical cells with an accuracy of ca. 97%, while human classification reproducibility is ca. 95%. In addition, an attempt to assign a measure of atypia to individual cells is described.

Cell Nucleus

Computerized nuclear morphometry as an objective method for characterizing human cancer cell populations.

A new method for measuring differences in nuclear detail in chrome alum gallocyanin-stained nuclei of cells from human breast cancers was compared with conventional subjective grading and classification systems. The new method, termed computerized nuclear morphometry (CNM), gives a multivariate numerical score that correlates well with nuclear atypia and gives a higher reproducibility of classification than do subjective observations with conventional histological preparations. When 100 individual nuclei from each of 137 breast cancers were examined by CNM, there was a broad CNM score variation between patients but a good reproducibility for each tumor. When different parts of the same tumor were sampled, there was good reproducibility between samples, indicating that some breast cancers at least are "geometrically monoclonal." When these cancers were compared by the grading systems of WHO and Black, correlations of 0.43 and 0.48, respectively, were found. There was a poor correlation between CNM and classifications of tumor type, but in general there were high values for CNM in medullary tumors and low values in mucous tumors. Correlations between CNM and tumor progression and prognosis await future study of patients participating in the study.

Breast Neoplasms

A software system to record and analyze digitized cell images.

This paper describes basic software for digitization and processing of microscopic cell images used at the Department of Clinical Cytology at Uppsala University Hospital. A family of programs running on a PDP-8 minicomputer which is connected to a Leitz Orthoplan microscope with two image scanners, one diode-array scanner and a moving-stage photometer, is used for data collection. The digitized image data is converted by converted by conversion program to IBM compatible format. The data structures for image processing and statistical evaluation on the IBM system are also described. Finally, some experiences from the use of the software in cytology automation are discussed.

Cell Biology