[Scholarship report: study trip to the USA].
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Biomedical subjects
Publications and source records attributed to M Nilsson.
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It has been shown that melanin has the properties of a polyanion and may in vivo and in vitro bind inorganic cations and drugs which are positively charged at physiological pH by a cation-exchange mechanism. In the present study, we explored if the organic aliphatic polycation spermidine would bind to melanin in vivo after administration of 14C-spermidine to pigmented mice and in vitro at incubation with pigment from beef-eyes. The results showed a high labelling of the pigmented tissues in the mice after the administration of 14C-spermidine. At long survival intervals, the radioactivity in the melanin was higher than in any other tissue. A strong melanin affinity of 14C-spermidine was found in vitro. An analysis of the binding by the method of Scatchard showed that the data could be best fitted by the assumption of two classes of binding sites. The in vivo bound material could be displaced by in vitro incubation in solutions containing inorganic cation-chloride salts or HCl and HCl was also very effective in inhibiting the melanin-binding of 14C-spermidine in vitro. The results indicate that an electrostatic interaction between spermidine and melanin will occur both in vivo and in vitro.
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We describe a solid-phase enzyme immunoassay for human serum ferritin, with the use of polyethylene glycol to shorten the reaction. The amount of bound enzyme-antibody conjugate used as a second site antibody is proportional to the ferritin titre in the assay. This method is fast, and the reagents are stable for many months at 4 degrees C. The lowest detectable concentration was 5 micrograms/l. Interassay coefficients of variation were 9.3 and 12.2%, respectively, at ferritin concentrations of 100 micrograms/l and 200 micrograms/l. The data also show that polyethylene glycol accelerates antigen-antibody complex formation in the solid phase. An assay may be completed in 5 h.
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125I-Labelled asialo-fetuin was taken up by isolated rat hepatocytes by a saturable process. Half maximum uptake was seen at about 3 - 10(-8) M asialo-fetuin. Non-parenchymal liver cells did not take up asialo-fetuin in vitro. Rate of uptake of asialo-fetuin exceeded rate of degradation at all concentrations of asialo-fetuin tested. Asialo-fetuin consequently accumulated in the cells until the extracellular supply was exhausted. Asialo-fetuin degradation could be studied without concurrent uptake by incubating cells, previously exposed to asialo-fetuin, in asialo-fetuin-free medium. Degradation, as evidenced by increase in acid-soluble radioactivity, was inhibited by NH4Cl and chloroquine. The change with time in the intracellular distribution pattern of radioactivity in cells that had been exposed to 125I-labelled asialo-fetuin for 10 min was examined by means of differential centrifugation. Initially, the radioactivity was found mostly in the microsomal fraction. 60 min after the exposure to labelled protein, the distribution pattern of radioactivity resembled that of the lysosomal enzyme beta-acetylglucosaminidase. The possibility that asialo-fetuin digestion takes place in lysosomes is discussed.
The uptake of formaldehyde-treated 125I-labelled human serum albumin in rat hepatocytes and nonparenchymal liver cells was measured in vivo and in vitro. Isolated liver cells were prepared by treating the perfused liver with collagenase. Purified hepatocytes and nonparenchymal cells were obtained by differential centrifugation. Human serum albumin was found to be taken up exclusively or almost exclusively by nonparenchymal cells in vitro and in vivo (after intravenous injection). The maximal rate of human serum albumin-uptake in vitro was comparable to that in vivo. Nonparenchymal cells degraded human serum albumin in vitro as indicated by release of trichloroacetic acid-soluble radioactivity. Degradation started about 20-30 min after addition of human serum albumin to cells and rate of degradation was proportional to rate of uptake. Human serum albumin-degradation could be studied without interference of concurrent uptake by separating cells that had been preincubated with human serum albumin from the medium and then reincubating them with human serum albumin-free medium. The lag phase before human serum albumin-degradation starts and the inhibitory effect of chloroquine on degradation indicate that human serum albumin is degraded in lysosomes. The data obtained show that enzymatically prepared nonparenchymal liver cells retain their endocytic activity in vitro. Denatured human serum albumin should be useful both as a marker for rat liver macrophages and for the study of intracellular proteolysis in these cells.
The mean absorbed dose in radiography of the breast with industrial film (Mamoray T3, Agfa-Gevaert), the Lo-dose system (Du Pont) and a new screen-film combination (MR 50-Mamoray RP 3, Agfa-Gevaert) was determined. The mean values were 17,2 and 1 mGy, respectively. Thus, the absorbed dose was considerably reduced by using the screen-film combination. This is of utmost importance as the potential risk of inducing malignancy is remarkably reduced, probably negligible.
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1. Lecithin:cholesterol acyltransferase is secreted from isolated rat heptocytes. 2. The secretion is stimulated when serum is added to the incubation medium. 3. Optimal conditions for secretion are: 5-10(6) hepatocytes per ml, 5 h incubation, pH 7.3-7.4 and 25% serum in the incubation medium. 4. Concomitantly with the secretion of lecithin:cholesterol acyltransferase there is a secretion of unesterified cholesterol and triacylglycerol. 5. Colchicine or cycloheximide in the incubation medium inhibits secretion of lecithin:cholesterol acyltransferase.
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The personality profile of 26 adult migraine patients from a large Swedish family with migraine and 87 controls were studied by means of Cloninger's seven-factor model of Temperament and Character (TCI; Temperament and Character Inventory). For the diagnosis of migraine, a questionnaire, slightly modified to fit the criteria according to the AD HOC committee on the classification of headaches of the International Headache Society, was used. The TCI assesses four dimensions of temperament, including novelty-seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (P), and three dimensions of character, including self-directedness (SD), co-operativeness (C) and self-transcendence (ST). Psychiatric morbidity did not differ between this family and the general population. One migraine patient had double depression (dysthymia and recurrent depression) and one had a personality disorder. No significant difference could be found in the higher order dimensions of temperament (NS, HA, RD and P) and character (SD, C and ST) between migraine patients and controls. However, on the subscale level, NS showed a slightly higher average in NS1 (exploratory excitability) and a significantly higher (p = 0.0448) average in NS2 (impulsivity) in migraine patients compared to controls. Somatic anxiety has been shown to be positively correlated with NS, and especially impulsivity. Our results showed a tendency of this personality profile, and may suggest an association between migraine and somatic anxiety.
Astroglia have the capacity to monitor extracellular glutamate (Glu) and maintain it at low levels, metabolize Glu, or release it back into the extracellular space. Glu can induce an increase in astroglial cell volume with a resulting decrease of the extracellular space, and thereby alter the concentration of extracellular substances. Many lines of evidence show that K(+) can be buffered within the astroglial gap-junction-coupled network, and recent results show that gap junctions are permeable for Glu. All these events occur dynamically: the astroglial network has the capacity to interfere actively with neurotransmission, thereby contributing to a high signal-to-noise ratio for the Glu transmission. High-quality neuronal messages during normal physiology can then be maintained. With the same mechanisms, astroglia might exert a neuroprotective function in situations of moderately increased extracellular Glu concentrations, i.e., corresponding to conditions of pathological hyper-excitability, or corresponding to early stages of an acute brain injury. If the astroglial functions are failing, neuronal dysfunction can be reinforced.