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Biomedical subjects

A Nilsson

Publications and source records attributed to A Nilsson.

At least 379 records · Page 21Linked to original sources

Absorption and metabolism of [3H]arachidonic and [14C]linoleic acid in essential fatty acid-deficient rats.

[3H]arachidonic acid (20:4) and [14C]linoleic acid (18:2) were fed in a triolein emulsion to essential fatty acid-deficient (EFAD) rats and to age-matched controls. Tissues were analyzed for radioactivity of different lipid classes after 1, 2, and 4 h. As in earlier studies [Nilsson and Melin. Am. J. Physiol. 255 (Gastrointest. Liver Physiol. 19): G612-G618, 1988], control rats retained more [3H]20:4 than [14C]18:2 in all organs except adipose tissue. In EFAD rats, recovery of [14C]18:2 was increased in small intestine, liver, heart, and kidneys. In comparison to controls, EFAD rats retained much more [14C]18:2 in phospholipids of these organs. The increase in the incorporation of both 3H and 14C into phosphatidylethanolamine was particularly pronounced. Another striking feature was the drastic increase in the retention after 4 h of 14C in cardiolipin, which is specifically located in the inner mitochondrial membrane. In contrast, incorporation of both 3H and 14C into phosphatidylinositol was decreased or unchanged in EFAD rats. Although fecal fat excretion was increased there was no evidence for a malabsorption or an increased retention in intestinal triacyglycerol of the radioactive fatty acids in EFAD rats. The proportion of [14C]18:2 that had been converted to [14C]20:4 was generally low but increased significantly with time in the liver and intestine of EFAD rats.

Aging↗

Chain elongation of fatty acids in rat small intestine: subcellular localization and effects of clofibrate and partially hydrogenated fish oil.

Clofibrate treatment was found to increase by a factor of two the activity of malonyl-CoA-dependent palmitic acid chain elongation in crude 'microsomal' fractions isolated from rat small intestine. A slight stimulation was indicated also after feeding a high fat diet containing partially hydrogenated fish oil (PHFO). This effect was, however, not statistically significant. Subcellular localization of this chain elongation activity was studied by Nycodenz gradient centrifugation. Chain elongation of palmitic acid was observed only in fractions containing high esterase activity, suggesting a microsomal localization. Similar distributions were seen after feeding the peroxisomal proliferators clofibrate and PHFO. Chain-shortening activity was found in the fractions containing high catalase activity, confirming our earlier studies suggesting a peroxisomal localization of this activity also in rat small intestine.

Acetyltransferases↗

Steroid hormone receptors in human adipose tissues.

Administration of glucocorticoid, estrogen, and progesterone is followed by changes in human adipose tissue distribution, morphology, and function. Therefore, specific receptors for these hormones were determined in different regions of human adipose tissue using ligand techniques, with separation of bound and free hormone by chromatography, absorption techniques, or isoelectric focusing, as well as protein quantitation with monoclonal antibodies against human estrogen and progesterone receptors. Furthermore, mRNAs were measured by solubilization hybridization technique with glucocorticoid, estrogen, and progesterone receptor cRNA probes for human receptors. Saturable specific cytosolic glucocorticoid binding was found. Quantitative analyses indicated more binding sites and mRNAs in intraabdominal than sc adipose tissue samples. In contrast, neither specific estrogen or progesterone binding, cytosolic or nuclear receptor protein, nor mRNAs for these receptors could be identified in abdominal, femoral, or omental adipose tissues. Parallel control experiments confirmed the presence of both estrogen and progesterone receptors in rat adipose tissues. It was concluded that while glucocorticoid receptors are clearly present in human adipose tissues, female sex hormone receptors are not present in quantities detectable with presently available methods. Effects of these hormones on human adipose tissue might, therefore, be mediated via a minute nondetectable quantity of receptors, the glucocorticoid receptor, or indirect mechanisms.

Adipose Tissue↗

Regulation by GH of insulin-like growth factor-I mRNA expression in rat epiphyseal growth plate as studied with in-situ hybridization.

Expression of insulin-like growth factor I (IGF-I) mRNA and its dependence on GH was studied in rat epiphyseal growth plate by in-situ hybridization. Methodological aspects of the technique were first evaluated on fixed sagittal cryosections from 28-day-old rat epiphyseal growth plates to ascertain specific hybridization. In-situ hybridization was compared on sections from 10- and 28-day-old rats and the GH-dependence was studied in 35-day-old hypophysectomized rats. Expression of IGF-I mRNA was apparent in chondrocytes of the proliferative, hypertrophic and early degenerative zones of the growth plate of 28-day-old rats. The epiphyseal growth plate from 10-day-old rats showed a weak hybridization signal compared with 28-day-old rats. In contrast, the mesenchymal cells of the periosteum of 10-day-old rats showed a rather strong hybridization signal. Hypophysectomy resulted in a reduction in hybridization signal and cell number of the growth plate compared with 35-day-old age-matched normal rats. GH-Replacement therapy (200 micrograms GH s.c. every 4 h for 24 h) resulted in partially restored expression of IGF-I mRNA. The present study has shown that the IGF-I gene is expressed in the rat epiphyseal growth plate chondrocytes and that the expression is dependent on GH. The results support a paracrine/autocrine role of IGF-I for the expression of the stimulatory effect of GH on longitudinal bone growth.

Animals↗

Smoking and inflammatory bowel disease: comparison with systemic lupus erythematosus. A case-control study.

Smoking is rare in patients with ulcerative colitis (UC). Onsets are common after stopping smoking. Several observations suggest possible immunologic mechanisms in UC. As smoking has an immunosuppressive effect, a possible role of smoking in UC could be immunosuppression. In this study an analogous hypothesis was investigated by studying smoking habits in patients with systemic lupus erythematosus (SLE), an inflammatory multisystemic disease of unknown etiology, characterized by disturbances in cellular and humoral immunity. At onset, 23 of 56 patients were smokers and 2 probable smokers. Few were ex-smokers. The patients were matched for age, sex, and geographic vicinity, and multiple relative risks were calculated. No correlation could be found between smoking/ex-smoking and SLE either at diagnosis or at interview, and no resemblance in habit to patients with UC was found. The present study provides no evidence that the immunosuppressive effect of smoking is sufficient to influence the clinical course of SLE and therefore by analogy does not support an immunosuppressive explanation of the possible protective effect of smoking in UC.

Adult↗

Hydrolysis of phosphatidylinositol by human pancreatic phospholipase A2.

Pure human pancreatic phospholipase A2 efficiently hydrolyzed the 2-ester bond of 14C-2-linoleoyl and 14C-2-arachidonyl phosphatidylinositol (PI). The rate of hydrolysis varied markedly with the bile salt (sodium taurocholate to sodium taurodeoxycholate, 3:4 mol/mol) concentration, the hydrolysis being decreased with increasing bile salt to PI ratio. The influence of bile salts was thus similar to that which has earlier been described for the hydrolysis of phosphatidylcholine (PC) with pig pancreatic phospholipase A2. When 2-3H-arachidonyl PC and 2-14C-arachidonyl PI were incorporated into a mixed substrate, PI was hydrolyzed even faster than PC, the hydrolysis of both phospholipids varying in the same manner with bile salt concentration. 2-14C-arachidonyl PI was also efficiently hydrolyzed by human duodenal content, although at a somewhat slower rate than 2-3H-arachidonyl PC. It is concluded that PI is a good substrate for human phospholipase A2. This minor but arachidonate-rich dietary phospholipid may thus be digested and absorbed by pathways similar to those of the major dietary and bile phospholipid, phosphatidylcholine.

Bile Acids and Salts↗

One hundred impotent men.

One hundred men complaining of poor or absent erectile capacity were investigated with a multidisciplinary approach. Their median age was 47 years. Mainly organic causes of the erectile failure were found in 27 and mainly psychologic in 40 cases, while factors of both types contributed in 33 cases. Vascular disorder was present in 20 men, including (functional) vasoconstriction in eight. Among 24 men with serum testosterone below 15 nmol/l the incidence of arterial disease, alcoholism and partner-related problems was significantly higher than in those with higher testosterone levels. Most psychologic factors were in general intrapsychic (affecting only the patient himself), while a minority were dyadic (related to the partner).

Erectile Dysfunction↗

Radiostrontium-induced oncogenesis and the role of immunosuppression. II. Influence of 90Sr dose, adult thymectomy and antilymphocyteglobulin treatment on the development of lympho-reticular and extraskeletal, neoplastic lesions in CBA mice.

The significance of depressed immune function for the development and progression of tumours induced by 90Sr (mainly osteosarcomas and malignant lymphomas) was investigated in a series of experiments by comparing the tumour responses in normal mice with those in immunocompromised mice. The present paper (part II) reports on lympho-reticular (LR) and extraskeletal neoplastic lesions in male CBA/SU mice after exposure to different single doses of 90Sr with or without additional immunosuppression by adult thymectomy (ATx) and/or prolonged antilymphocyteglobulin (ALG) treatment. Neoplastic lesions in bone were reported in part I. The status of the animal's immune system and responsive ability were examined in parallel experiments. The tumour yields were analysed in relation to the dosage of 90Sr and the immunosuppressive treatments employed. Although the incidences and latency times of induced tumours were clearly dose-dependent, they were never significantly influenced by ATx/ALG treatments. Thus, no substantial support was gained for the theory that the immune system plays a controlling or modifying role in 90Sr carcinogenesis. The results, which are in agreement with the bone tumour responses, suggest that 90Sr induced tumours either do not express the antigens necessary for immune rejection or that the decline in immune responsiveness induced by ATx/ALG was of little consequence for tumour development and spread. The pathogenesis of 90Sr induced malignant lymphomas (MLs) and their immunophenotypes are discussed.

Animals↗

EMLA for pain relief during arterial cannulation. A double-blind, placebo-controlled study of a lidocaine-prilocaine cream.

The aim of the study was to evaluate the effect of a lidocaine-prilocaine cream (EMLA cream, Astra) in relieving pain during arterial cannulation. The study had a random, double-blind, placebo-controlled design and included altogether 90 patients. All the patients were premedicated with an opioid before cannulation. An EMLA application time of 60 minutes was used in 60 patients (30 EMLA/30 placebo) and there was no difference in the pain reaction measured on a visual analogue scale (VAS) or on an observer's verbal scale. The study was extended with a further 30 patients (15 EMLA/15 placebo) with an application time exceeding 90 minutes. Between these groups pain experience measured by VAS did not show any significant difference although the mean value was lower in the EMLA group. Observer ratings showed a significant (p less than 0.01) difference in distribution towards lower ratings in the EMLA group. In conclusion EMLA was found to have a weak, but measurable effect when the application time exceeded 90 minutes but not after 60 minutes.

Anesthetics, Local↗

Internalization of retinol-binding protein in parenchymal and stellate cells of rat liver.

We have studied uptake of retinol-binding protein (RBP) by rat liver cells. First, we compared the in vivo uptake in different liver cells of 125I-labeled RBP with that of other well-known ligands. We found that the ligands studied were recognized differently by the various cell types in the liver, and that RBP was most efficiently taken up by parenchymal and stellate cells. We then studied the in vivo uptake of RBP in liver cells by immunocytochemistry at the electron microscopic level using ultrathin cryosections. Ten min after injection, RBP was localized to parenchymal cells and stellate cells. In these cells, RBP was detected on the cell surface and in vesicles near the cell surface. RBP was observed mainly in association with the membrane in these vesicles. Two hours after injection, RBP was localized not only on the cell surface and in vesicles close to the cell surface, but also in larger vesicles located deeper in the cytoplasm of these cells. RBP in larger vesicles was observed at a distance from the vesicular membrane. Finally, we compared the distribution of endocytosed RBP in liver parenchymal cells with that of asialo-orosomucoid, a ligand known to be internalized by receptor-mediated endocytosis. We detected both ligands on the cell surface and in small vesicles located close to the cell surface and in larger vesicles located deeper in the cytoplasm. Asialo-orosomucoid and RBP were seldom observed in the same small vesicles, but the larger vesicles contained both ligands. These data suggest that RBP is internalized in parenchymal and stellate cells of the liver by receptor-mediated endocytosis.

Animals↗

A 62 kDa protein is photoaffinity labelled by [3H]felodipine in vascular smooth muscle, but not in cardiac and skeletal muscle.

Irradiation of a cytosolic fraction from vascular smooth muscle in the presence of [3H]felodipine resulted in the labelling of a protein with an apparent molecular weight of 62 kDa. The labelling was seen on UV-irradiation at 360 nm, but not at 254, 278 or at wavelengths above 410 nm. The photolabelling was enhanced in the absence of oxygen. In cytosolic fractions prepared from porcine liver, cardiac and skeletal muscle no photoaffinity labelling of proteins between 90 and 45 kDa could be demonstrated. The results suggest that felodipine is a photoaffinity ligand and that felodipine binds to a soluble protein present in vascular smooth muscle but not in the other tissues tested.

Affinity Labels↗

Hydrolysis of triacylglycerol arachidonic and linoleic acid ester bonds by human pancreatic lipase and carboxyl ester lipase.

The hydrolysis of polyenoic fatty acid ester bonds with pure human colipase-dependent lipase, with carboxyl ester lipase (CEL) and with these enzymes in combination was studied, using [3H]arachidonic- and [14C]linoleic acid-labelled rat chylomicrons as a model substrate. During the hydrolysis with colipase-dependent lipase, the amount of 3H appearing in 1,2-X-diacylglycerol (DG) markedly exceeded that of 14C. When CEL was added in addition this [3H]DG was efficiently hydrolyzed. CEL alone hydrolyzed the triacylglycerol (TG) at a low rate. The hydrolysis pattern with human duodenal content was similar to that seen with colipase-dependent lipase and CEL in combination. Increasing the concentration of taurodeoxycholate (TDC) and taurocholate (TC) or of TDC alone stimulated the hydrolysis of [3H]- and [14C]TG, but increased the accumulation of labelled DG that could act as substrate for CEL. It is suggested that very-long-chain polyenoic fatty acids of DG formed during the action of the colipase-dependent lipase on TG containing these fatty acids may be a physiological substrate for CEL.

Arachidonic Acid↗

Low-density-lipoprotein receptors in different rabbit liver cells.

Receptor-dependent uptake mechanisms for low-density lipoprotein (LDL) were studied in rabbit liver parenchymal and non-parenchymal cells. Hybridization studies with a cDNA probe revealed that mRNA for the apo (apolipoprotein) B,E receptor was present in endothelial and Kupffer cells as well as in parenchymal cells. By ligand-blotting experiments we showed that apo B,E-receptor protein was present in both parenchymal and non-parenchymal cells. Studies of binding of homologous LDL in cultured rabbit parenchymal cells suggested that about 63% of the specific LDL binding was mediated via the apo B,E receptor. Approx. 47% of the specific LDL binding was dependent on Ca2+, suggesting that specific Ca2+-dependent as well as Ca2+-independent LDL-binding sites exist in liver parenchymal cells. Methylated LDL bound to the parenchymal cells in a saturable manner. Taken together, our results showed that apo B,E receptors are present in rabbit liver endothelial and Kupffer cells as well as in the parenchymal cells, and that an additional saturable binding activity for LDL may exist on rabbit liver parenchymal cells. This binding activity was not inhibited by EGTA or reductive methylation of lysine residues in apo B. LDL degradation in parenchymal cells was mainly mediated via the apo B,E receptor.

Animals↗

The influence of different insulin regimens on quality of life and metabolic control in insulin-dependent diabetics.

Administration of insulin with premeal boluses of short-acting insulin using a new injection device (Novopen) was compared with a conventional three times daily injection regimen regarding aspects of quality of life and metabolic control in insulin-dependent diabetes mellitus (IDDM). Eighteen C-peptide-negative patients with IDDM (16 men, two women, aged 31.0 +/- 7.4 years, duration of diabetes 13.0 +/- 4.6 years; mean +/- SD) participated in the study. All patients had been treated with three daily insulin injections for at least 1 year prior to the study. The patients were randomized into two groups. Group A started a 3-month treatment period with premeal injections of short-acting insulin and intermediate-acting insulin at bedtime. This period was followed by another 3 months using the initial three times daily injection regimen. Group B completed the study in the reverse order. Quality of life was assessed by using questionnaires and personal interviews by the same clinical psychologist. Metabolic control was assessed by measuring the levels of glycosylated hemoglobin. The results show that both treatment groups experienced a general improvement in mood and well-being during the period with multiple insulin injection treatment. Furthermore, during the periods of insulin pen treatment, an increased experience of freedom and less dependence on fixed meal times were noted. Overall metabolic control, insulin dosage, body weight, and number of hypoglycemic episodes did not change during the study. It is concluded that metabolic control, safety, and number of hypoglycemic episodes using premeal doses of short-acting insulin using Novopen were not different from those seen during conventional treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗