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Biomedical subjects

A Nilsson

Publications and source records attributed to A Nilsson.

At least 307 records · Page 17Linked to original sources
PubMed1993

Establishment of a growth hormone responsive chondrogenic cell line from fetal rat tibia.

Reproducible effects of growth hormone (GH) on primary isolated cells in monolayer are highly dependent on the culture conditions and/or the fraction of GH responsive cells. To study the effect of GH at the cellular level, a homogenous cell line with both GH responsiveness and chondrogenic properties was established. Primary isolated cells from 18-day-old fetal rat tibia were subcultured using a strict protocol for passages (every third day and a seeding density of 15,000/cm2). Of six established cell lines, one fetal tibia cell line No. 5 (FTC 5) expressed adipogenic and chondrogenic properties at a low frequency. Cells from FTC 5 were subcultured in soft agar suspension with the addition of bovine GH (100 ng/ml). After 14 days in culture eight monoclonal cell lines were established from individual large colonies. Two subclones, FTC 5:3 and FTC 5:6, expressed a chondrogenic phenotype as demonstrated by chondrocyte foci, alcian blue staining and production of type II collagen. Further characterization of FTC 5:3 revealed specific binding of bovine GH with an affinity of 1.7 x 10(9) M-1, and approximately 7300 receptors/cell. Northern blot analysis of FTC 5:3 with a 32P-labeled RNA probe complementary to an extracellular part of the rat GH receptor, revealed two major labeled bands (4.0 and 1.2 kilobases). Both GH and insulin-like growth factor-I (IGF-I) stimulated 3H-thymidine uptake in FTC 5:3 (194 +/- 28% and 405 +/- 127% over control, respectively), while proteoglycan synthesis, as measured by [35S]sulphate uptake, was stimulated by IGF-I only (101 +/- 18% over control).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Does the bile salt-stimulated lipase of human milk have a role in the use of the milk long-chain polyunsaturated fatty acids?

Long-chain polyunsaturated (LCP) fatty acids derived from linoleic (18:2 n-6) and alpha-linolenic (18:3 n-3) acids are considered essential nutrients in preterm infants. The efficiency by which such fatty acids are released as absorbable products from triacylglycerol was explored in vitro using rat chylomicron triacylglycerol as substrate. When incubated with purified human pancreatic colipase-dependent lipase and colipase, arachidonic acid (20:4 n-6) was released less efficiently than linoleic acid from such triacylglycerol. This difference was not seen when purified human milk bile salt-stimulated lipase (BSSL) was incubated with the triacylglycerol substrate, and it was almost abolished when colipase-dependent lipase (with colipase) and BSSL acted simultaneously, as they do in breast-fed infants. There was no difference in arachidonic acid and eicosapentaenoic acid (20:5 n-3) release rates with either colipase-dependent lipase or BSSL, albeit the release was more rapid with the milk enzyme than with colipase-dependent lipase. Again, the most efficient release as absorbable free fatty acids was achieved when the two lipases operated together. The relative resistance to hydrolysis of arachidonic acid and eicosapentaenoic acid by colipase-dependent lipase was best explained by the localization of the first double bond to the delta-5 position of the respective fatty acid. The results obtained suggest that BSSL is of importance for the efficient use of human milk LCP fatty acids.

Animals↗
PubMed1993

Pharmacokinetics of budesonide enema in patients with distal ulcerative colitis or proctitis.

Pharmacokinetic data obtained after one dose of a 2-mg budesonide enema were compared with data obtained after the last dose of four weeks of daily treatment in 24 patients with active distal ulcerative colitis or proctitis. This open multicentre study involved 28 eligible patients. Sigmoidoscopy and biopsy scores improved significantly (P < 0.002) during the four-week treatment period. Maximal plasma concentration (Cmax) of budesonide was 2.1 nmol/L 1.3 h after the first dose and 2.5 nmol/L 1.2 h after the last dose; the difference was not significant. The area under the curve (AUC) of plasma concentration vs. time was after the first dose 9.7 nmol h/L and after the last dose 11.6 nmol h/L (P < 0.03). The small increase in AUC may be attributed to improved absorption. During the last dose interval, minimal plasma concentration was below the limit of quantitation in most subjects. The Cmax and AUC of budesonide increased slightly after four weeks of treatment, but budesonide did not accumulate. Mean morning plasma cortisol values did not change significantly during treatment (P = 0.083), although a small change in cortisol levels between the first visit (pre-treatment) and last visit was positively correlated to the Cmax of budesonide measured at the last visit (P = 0.012).

Administration, Topical↗
PubMed1993

Acute puerperal breast abscesses: US-guided drainage.

Breast abscesses typically develop in lactating women. The recommended treatment is surgical incision and drainage with the patient under general anesthesia. Ultrasonically guided percutaneous drainage with local anesthesia was performed in 19 consecutive patients referred for treatment because of clinical signs of acute puerperal breast abscess. Eighteen of the 19 patients (95%) were successfully treated. Long-term follow-up (median, 12 months) did not show any recurrences, and the cosmetic results were excellent. Eight of the 19 patients (42%) continued nursing during and after treatment. Ten of the 19 (53%) were treated on an outpatient basis. On the basis of these results, the authors recommend ultrasonically guided percutaneous treatment for use in patients with acute puerperal breast abscesses.

Abscess↗
PubMed1993

Two-year carcinogenicity study with sennosides in the rat: emphasis on gastro-intestinal alterations.

A carcinogenicity study was conducted by administering a purified senna extract via the drinking water to Sprague-Dawley rats of each sex for 2 years. The daily doses received were 0, 5, 15 and 25 mg/kg. Histopathological examination was restricted to tissues from the gastro-intestinal tract, liver, kidneys, adrenals and from tissues with any observed abnormalities or masses. A laxative effect was observed in high-dose females, and in mid- and high-dose males. No significant differences in survival were found between treated and control groups. Mean body weight gain was significantly decreased in high-dose males. Increased kidney weights were noted in mid-dose males and females, and high-dose females. Histopathological examination of control and high-dose rats did not indicate any difference in the incidence of neoplastic lesions. As regards non-neoplastic lesions, a treatment- but not dose-related increase in reactive mesenteric lymph node hyperplasia was observed in preterminally sacrificed rats. However, a corresponding increase was not noted in the terminally sacrificed rats or when preterminal and terminal animals were combined. No ultrastructural changes in the myenteric nerve plexus of the colon and jejunum could be detected in the small number of investigated tissue samples. In conclusion, results from the present investigation do not indicate any relationship between long-term administration of purified senna extract and gastrointestinal, liver, kidney or adrenal tumors in the rat.

Animals↗
PubMed1993

Expression of insulin-like growth factor-I (IGF-I) in the rat fallopian tube: possible autocrine and paracrine action of fallopian tube-derived IGF-I on the fallopian tube and on the preimplantation embryo.

Recent studies have indicated that growth factors such as insulin-like growth factors (IGFs) increase the growth rate of cultured preimplantation embryos. We therefore hypothesized that the fallopian tube may produce IGFs which in turn participate in the regulation of preimplantation embryo development in vivo. In the present study we examined the expression of IGF-I in the fallopian tube. We demonstrated that IGF-I transcripts (7.0, 1.7, and 1.2-0.8 kilobases) were abundant in the fallopian tube. Immunoreactive IGF-I was most abundant in the epithelial cells in the fallopian tube, and IGF-I messenger RNA (mRNA) was detected in the luminal region of the fallopian tube. A solution hybridization assay was used to examine the regulation of IGF-I mRNA. The abundance of IGF-I transcripts changed markedly during the 4-day estrous cycle with the highest levels on the day of proestrus. The increase in IGF-I mRNA between the day of diestrus II and the day of proestrus was 4-fold (P < 0.01). The pattern of IGF-I mRNA expression in the fallopian tube resembled the pattern of ovarian estrogen production during the estrous cycle. The level of IGF-I mRNA decreased after hypophysectomy. The expression of IGF-I mRNA in the fallopian tube was dose-dependently regulated by estradiol, and a single sc injection of estradiol [5 micrograms/100 g body wt (BW)] increased the IGF-I mRNA in a time-dependent manner with a significant increase after 3 h (P < 0.01). The lowest estradiol dose tested (0.1 microgram/100 g BW) increased the expression after 6 h, whereas progesterone (5 micrograms/100 g BW) was ineffective. The presence of embryos in the fallopian tube did not statistically significantly influence the abundance of IGF-I transcripts as measured with a solution hybridization assay on RNA extracted from whole fallopian tubes. In order to determine possible targets for fallopian tube-derived IGF-I we examined the expression of IGF-I receptor mRNA. Northern blot analysis revealed that an 11-kilobase IGF-I receptor transcript was expressed in the fallopian tube. Using a reverse transcriptase-polymerase chain reaction, IGF-I receptor mRNA was also detected in the eight-cell but not two-cell preimplantation embryo. The present study demonstrates that IGF-I is produced in the fallopian tube and its expression is regulated by estradiol. Both the fallopian tube and the eight-cell preimplantation embryo express IGF-I receptors and are therefore potential target tissues.

Animals↗
PubMed1993

Embryonic stem cells express growth hormone receptors: regulation by retinoic acid.

Embryonic and fetal growth are generally considered to be independent of pituitary GH. However, it has been demonstrated recently that 18-day-old rat embryos and rat fetuses express GH receptors, suggesting that GH could play a role in early development. The aim of the present investigation was to determine whether preimplantation embryos also express GH receptors. Germ line competent mouse embryonic stem (ES) cells and cultured mouse preimplantation embryos were examined with Northern blot analysis, RNAse-protection solution-hybridization assays, reverse transcription/polymerase chain reaction assays and immunohistochemistry for the detection of GH receptors. Northern blot analysis of ES cells using a probe corresponding to the extracellular domain of the GH receptor demonstrated the presence of two transcripts (1.2 and 4.5 kilobases). The RNAse-protection solution-hybridization assay revealed that ES cells express approximately one sixth of the GH-receptor messenger RNA (mRNA) levels expressed in liver from pregnant mice. Treatment of cultured ES cells with retinoic acid (100 nM) for 6 days increased GH-receptor mRNA levels (P < 0.01). GH-receptor mRNA was further identified in ES cells, preimplantation embryos, muscle, liver, and placenta by a reverse transcription/polymerase chain reaction assay. In humans it has previously been shown that exon 3 of the GH-receptor is deleted in the placenta. However, none of the studied mouse tissues had a deletion of the GH-receptor mRNA corresponding to exon 3 of the human GH receptor. GH-receptor immunoreactivity was identified on the cultured ES-cells by immunohistochemistry. In conclusion, we have in the present study shown that germline competent ES cells and preimplantation mouse embryos express the GH receptor transcript and that this transcription is increased by retinoic acid in ES cells. Furthermore, the presence of GH-receptor immunoreactivity on the ES cells indicates that the GH-receptor transcript is translated.

Animals↗
PubMed1993

A double-staining technique for detection of growth hormone and insulin-like growth factor-I binding to rat tibial epiphyseal chondrocytes.

In the present study a double-staining technique was developed to investigate simultaneous GH and insulin-like growth factor-I (IGF-I) binding to chondrocytes in a monolayer cell culture. Rat tibial epiphyseal chondrocytes were isolated by enzymatic digestion and cultured in monolayer. GH and IGF-I were labelled with biotin. The affinity of the biotin-labelled ligands was compared with unlabelled ligands in a radioreceptor assay. To study the distribution of GH and IGF-I binding in the monolayer, chondrocytes were incubated with biotinylated ligands with or without an excess of unlabelled ligands, followed by incubation with Vectastain ABC complex, which was then reacted with diaminobenzidine (DAB). Double staining was accomplished by carrying out the first reaction with DAB in the presence of nickel ammonium sulphate to give a black precipitate, followed by incubation with the second ligand, then ABC complex and finally DAB in the absence of nickel ammonium sulphate to give a brown stain. The presence of type-II collagen was demonstrated by immunohistochemistry and used as a marker for differentiated chondrocytes. Biotin-labelled GH and biotin-labelled IGF-I exhibited dose-dependent displacements of 125I-labelled GH and 125I-labelled IGF-I respectively from the chondrocytes in a radioreceptor assay. The displacement curves were identical to those of unlabelled ligands indicating that the affinity was unaltered. Binding of biotinylated GH to cells was seen throughout the culture in regions where there was little or no type-II collagen staining. IGF-I binding was predominantly localized to cells at high density; areas which also showed a high degree of staining for type-II collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Plasmapheresis in the treatment of primary septic shock in humans.

14 patients (mean age 25.5 yrs) with life-threatening primary septic shock were eligible for treatment with acute plasmapheresis in a prospective study. They had a short history of sepsis and had no severe underlying disease. 10/14 patients had systemic meningococcal disease. All patients were severely ill with a mean APACHE II score of 25.0. 12/14 patients were treated with plasmapheresis exchanging 1 plasma volume within hours of admission. 11/14 patients survived without major sequelae and 3 (21%) died of irreversible septic shock. This mortality is lower than that predicted from the APACHE II scores (55.2%). A subgroup of plasmapheresis-treated patients with septic shock and extensive petechiae were compared to a historical control group. The mortality in the treatment group was 1/7 (14%) versus 8/21 (38%) in the control group. We conclude that acute plasmapheresis may be a therapeutic option in the early stages of severe primary non-surgical septic shock.

Adolescent↗
PubMed1993

Concentration-effect relationships of propofol after total intravenous anesthesia.

To evaluate the concentration-effect relationships of propofol during recovery after total intravenous anesthesia, 20 female patients undergoing lower abdominal surgery were studied. In 10 patients (Group B) the propofol infusion was supplemented with an epidural block with bupivacaine to evaluate the relation between the blood concentration of propofol and various pharmacodynamic end-points. The remaining 10 patients (Group A) received an alfentanil infusion intravenously instead of the epidural block to assess the dynamic interactions of alfentanil and propofol. Postoperative performances (drowsiness, amnesia, cooperation, and orientation) were evaluated by means of scoring scales. Critical flicker fusion threshold (CFF) also was used to assess the level of postoperative alertness. A propofol blood concentration of 2.5 micrograms/mL was required for satisfactory hypnosis during surgery and at 0.8 +/- 0.4 microgram/mL, the patients were considered fully awake. A concomitant alfentanil infusion reduced the propofol concentration required by 0.2-0.4 microgram/mL for the same degree of effect. Rapid recovery was seen in all patients, but in the group receiving alfentanil infusion there was a shift to the left of the concentration-effect curve in regard to drowsiness and a statistically significant prolongation of recovery by CFF-measurement which suggests a possible dynamic interaction with alfentanil. We conclude that there is a good correlation between the blood concentration of propofol and the pharmacodynamic responses during recovery.

Adult↗
PubMed1993

Human hepatoblastoma cells (HepG2) and rat hepatoma cells are defective in important enzyme activities in the oxidation of the C27 steroid side chain in bile acid formation.

We have examined the ability of HepG2 human hepatoblastoma cells and 7800 C1 Morris rat hepatoma cells to convert 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA) and 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid (DHCA) to cholic acid and chenodeoxycholic acid, respectively. Cell extracts from both these cell lines could neither form cholic acid from THCA nor from the activated form, THCA-CoA. This suggests that both cell lines are defective in two enzyme activities involved in the pathway, the microsomal THCA-CoA ligase and the peroxisomal THCA-CoA oxidase. Furthermore, we show that the subsequent enzymes are active in the conversion to bile acids, because the product of the THCA-CoA oxidase, 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholest-24-enoyl-coenzyme A (delta 24-THCA-CoA) or delta 24-THCA in the presence of THCA-CoA ligase, are converted to cholic acid by both cell lines. HepG2 cells were able to slowly form chenodeoxycholic acid and cholic acid from 5 beta-cholestane-3 alpha, 7 alpha-diol and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol, respectively, in 24- and 96-h incubations. The rate of cholic acid formation was lower than the rate for chenodeoxycholic acid and there was a clear accumulation of THCA. 7800 C1 Morris cells had no ability to form cholic acid or chenodeoxycholic acid after 96 h incubation. We conclude that these two cell lines have defects in two enzyme activities involved in the peroxisomal oxidation in bile acid formation, the microsomal THCA-CoA ligase and the peroxisomal THCA-CoA oxidase.

Animals↗
PubMed1993

Fatty acid composition of serum phosphatidylcholine in healthy subjects consuming varying amounts of fish.

Fatty acid composition of serum phosphatidylcholine was studied in subjects living in the same area and selected for high consumption of fat fish, high consumption of lean fish, moderate or no consumption of fish. The proportion of eicosapentaenoic acid (20:5) in serum phosphatidylcholine was fourfold higher, and that of docosahexaenoic acid (22:6) twofold higher among high consumers of fish compared to non-consumers, and these proportions were also higher in fat fish consumers than in high consumers of lean fish, and in moderate consumers compared to non-consumers. In the whole group the intake of fat fish was correlated to the proportions of 20:5, 22:6 and total n-3 fatty acids in serum phosphatidylcholine. The estimated intake of total n-3 fatty acids from fish was highly correlated to the proportions of these fatty acids in serum phosphatidylcholine (r = 0.87). Plasma triglyceride concentration was lower among high fat fish consumers than in other groups, but no differences between groups were observed for concentration of cholesterol, LDL cholesterol, and HDL cholesterol. It is concluded that subjects who consume high amounts of fat fish in their normal diet attain approximately the same proportions of n-3 fatty acids in serum phosphatidylcholine as reported for subjects taking fish oil supplements, and that fatty acid composition of serum lipids can be used as a marker of intake of fat fish.

Adult↗
PubMed1992

Growth hormone induces multiplication of the slowly cycling germinal cells of the rat tibial growth plate.

To study the effect of locally infused growth hormone (GH) or insulin-like growth factor I(IGF-I) on slowly cycling cells in the germinal cell layer of the tibial growth plate, osmotic minipumps delivering 14.3 microCi of [3H]thymidine per day were implanted s.c. into hypophysectomized rats, and GH (1 microgram) or IGF-I (10 micrograms) was injected daily through a cannula implanted in the proximal tibia. The opposite leg served as a control. After 12 days of treatment, the osmotic minipumps were removed, and three rats in each group were given GH (20 micrograms/day, s.c.) for an additional 14 days to chase the labeled cells out of the proliferative layers. Labeled cells remained in the germinal layer, in the perichondrial ring, and on the surface of the articular cartilage close to the epiphyseal plate. GH administered together with labeled thymidine significantly increased the number of labeled cells in the germinal cell layer compared to that in the control leg (ratio = 1.95 +/- 0.13), whereas IGF-I showed no stimulatory effect (ratio = 0.96 +/- 0.04). Therefore GH but not IGF-I stimulates the multiplication of the slowly cycling (label-retaining) cells in the germinal layer of the epiphyseal plate. IGF-I acts only on the proliferation of the resulting chondrocytes.

Animals↗
PubMed1992

Fish as a source of exposure to mercury and selenium.

In a total of 395 subjects with varying fish consumption habits, mercury levels in whole blood (B-Hg), and selenium levels in plasma (P-Se) were studied. Also, in subcohorts, mercury levels in blood cells (Ery-Hg; n = 79), plasma (P-Hg; n = 158) and urine (U-Hg; n = 125) were analysed. There were statistically significant associations between fish intake on the one hand, and B-Hg, Ery-Hg and P-Hg, on the other, but not so with U-Hg. In subjects who never had fish, the average B-Hg was 1.8 ng/g, in subjects who had at least two fish meals each week, 6.7 ng/g. Ery-Hg, and to a less extent P-Hg, were associated with levels of marine n-3 polyunsaturated fatty acids (PUFA) in serum phosphatidylcholine. P-Hg and U-Hg were associated with numbers of teeth with amalgam fillings. P-Se also correlated with fish intake. In subjects who never had fish, P-Se averaged 80 micrograms/l, in subjects who had at least two fish meals per week, 91 micrograms/l. There was an association between PUFA and P-Se. Further, there were statistically significant associations between P-Se on the one hand, and B-Hg, Ery-Hg and P-Hg on the other. The data clearly demonstrate the importance of fish for the exposure to methylmercury and selenium in the Swedish diet, and the impact of amalgam as a source of exposure to inorganic mercury.

Adult↗