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Biomedical subjects

L Carlsson

Publications and source records attributed to L Carlsson.

At least 145 records · Page 8Linked to original sources
PubMed1989

Establishment and functional implications of B-cell connectivity.

We have discussed some aspects of the structure of the normal immune system, particularly the B-cell compartment. We have argued: that a basic property of the natural antibody repertoire is constituted by high degrees of connectivity within the immune system as well as between the system and other components of the organism; that the complementarities constituting this connectivity are based on self-self interactions, high degrees of degeneracy or somatically selected interactions and that these properties are conserved through evolution, to ensure self-reference; that by evolutionary selection, antibody V-genes encoding such structural properties are ensured to be expressed early in ontogeny. The set of highly connected cells will be kept through ontogeny and form the basis for a compartment of naturally-activated lymphocytes making up 10-15% of the total lymphocyte population. As suggested before, this pool of connected cells may be responsible for maintenance of normal network dynamics and prevention of autoaggression.

Amino Acid Sequence↗
PubMed1989

Plasma growth hormone pattern regulates epidermal growth factor (EGF) receptor messenger ribonucleic acid levels and EGF binding in the rat liver.

It has recently been shown that GH increases the number of available hepatic receptors for epidermal growth factor (EGF). In the present study the effects of the sexually dimorphic plasma GH pattern (higher pulsatility in male rats) on hepatic EGF binding and EGF receptor mRNA concentration were investigated. The specific binding of [125I]EGF to purified liver membranes was about 2-fold higher in male rats than in females on days 35, 50, and 80 of life. EGF receptor mRNA levels, as determined by an RNase protection solution hybridization assay, were higher in males only on days 47-50. Hypophysectomy on day 50 reduced the EGF receptor mRNA concentration to a level that did not differ between male and female rats. In hypophysectomized rats of both sexes, intermittent GH treatment (sc injections every 12 h for 7 days) enhanced hepatic EGF receptor mRNA concentrations to normal male levels, while continuous GH administration was less effective. Northern blot analysis indicated that transcripts with apparent sizes of 9.5 and 6.6 kilobases were dependent on the plasma GH pattern. Intermittent iv GH replacement therapy for 5 days given at 3-h intervals by an automatic iv infusion system increased the hepatic EGF receptor mRNA concentration as well as specific EGF binding, whereas continuous iv GH infusion was ineffective. These results show that a pulsatile plasma GH pattern, similar to that of male rodents, is markedly more effective in enhancing hepatic EGF receptor mRNA levels and EGF binding than a continuous feminine GH pattern. These results are consistent with a pretranslatory stimulation of EGF receptor synthesis by pulsatile GH.

Animals↗
PubMed1989

Osseointegrated knee prostheses. An experimental study in rabbits.

Osseointegration, defined as direct bone-to-implant contact, has been suggested as an approach for improving the results of arthroplasties of the major joints. An experimental investigation in femoral-patellar joint of the rabbit was performed to evaluate whether osseointegration could be achieved in a one-stage surgical procedure. After three months, it was found that the screws used for anchorage of the prosthesis showed an average direct bone-to-implant contact of 60% in three selected consecutive threads on each side. The range was 40-90%. These figures correspond well with previously reported ones from bone anchored titanium fixtures. It was therefore concluded that osseointegration of dynamically loaded screws used for anchorage of a femoral-patellar joint prosthesis may be achieved in spite of the fact that no controlled healing period for the screws was observed.

Animals↗
PubMed1988

A crucial role of ongoing anaerobic glycolysis in attenuating acute ischemia-induced release of myocardial noradrenaline.

The myocardial energy requirements of the noradrenergic nerve terminal to retain its transmitter during acute myocardial ischemia were examined in the isolated perfused rat heart. In hearts perfused with glucose as exogenous substrate no increased release of noradrenaline (NA) could be detected during ischemia. In contrast, an increased efflux of NA was seen from glucose-perfused hearts when the glycolytic pathway was inhibited with 0.5 mM iodacetic acid. Accordingly, induction of ischemia in glycogen-depleted hearts (in the absence of exogenous substrate) or in hearts perfused with either lactate, pyruvate or acetate was also associated with a marked efflux of NA. However, no efflux was detected from glycogen-depleted hearts when glucose was present during the ischemic period. Uncoupling of oxidative metabolism with 0.1 mM 2.4-dinitrophenol did not cause any increased loss of NA during ischemia. In conclusion, these results demonstrate that severe restriction in coronary flow is accompanied by increased release of myocardial NA. Furthermore, maintainance of anaerobic glycolysis is of crucial importance for retention of the noradrenergic transmitter during ischemic conditions.

2,4-Dinitrophenol↗
PubMed1988

Nutritional rehabilitation in Bangladesh--the importance of zinc.

Our aim was to investigate whether zinc deficiency becomes apparent during nutritional rehabilitation and limits the rate of weight gain. Twenty-five severely malnourished children, who were admitted to the Children's Nutrition Unit in Bangladesh, were alternately allocated to two groups. Their mean dietary Zn intake was 3.7 mg/d and mean caloric intake greater than 150 kcal.kg-1.d-1; one group received a daily Zn supplement of 50 mg for 2 wk. During the first week, weight gain was similar in the two groups, but during the second week, weight gain was 73% more in the Zn-supplemented group (8.83 +/- 1.56 vs 5.09 +/- 1.62 g.kg-1.d-1). The 95% confidence limits were 0.88 less to 8.36 g.kg-1.d-1 more gain in children receiving Zn supplements. The results strongly suggest that Zn supplements are beneficial to severely malnourished children during nutritional rehabilitation. Polymorphonuclear (PMN) cell Zn increased in the group receiving Zn supplements (p less than 0.001), confirming that the Zn content of PMN cells reflects available Zn.

Bangladesh↗
PubMed1988

Pulsatile intravenous growth hormone (GH) infusion to hypophysectomized rats increases insulin-like growth factor I messenger ribonucleic acid in skeletal tissues more effectively than continuous GH infusion.

In this study we have investigated a possible functional role of the plasma pattern of GH in regulation of insulin-like growth factor I (IGF-I) mRNA in liver, skeletal muscle, and rib growth plate of the rat. Hypophysectomized male rats given T4 and glucocorticoid replacement therapy were equipped with indwelling jugular venous cannulae attached via swivels to a multichannel pumping system programmed to deliver human GH in a continuous or pulsatile (one pulse per 3 h) pattern for 5 days. At the end of the experiment, skeletal muscle, rib growth plates, and liver from intact and hypophysectomized rats were homogenized, and total nucleic acid was prepared. IGF-I mRNA was quantitated by solution hybridization assay using a RNA probe radiolabeled with [35S]UTP. Pulsatile treatment with GH in a dose of 1.5 U/kg.day induced a 3- to 5-fold increase in the levels of IGF-I mRNA in skeletal muscle and rib growth plates. In contrast, continuous infusion with GH was much less effective in these tissues. In the liver both continuous and pulsatile GH infusion significantly elevated the amount of IGF-I mRNA, and there was no significant difference between these two treatments. In the tissues studied similar results were obtained with a higher dose of GH (3.0 U/kg.day). Pulsatile GH treatment stimulated longitudinal bone growth more effectively than continuous GH treatment, confirming earlier studies. It is concluded that pulsatile GH treatment is more effective than continuous GH infusion in increasing IGF-I mRNA levels in rib growth plate and skeletal muscle, i.e. two major target organs for the anabolic effects of GH.

Animals↗
PubMed1988

Implant fixation improved by close fit. Cylindrical implant-bone interface studied in rabbits.

Cylindric titanium implants of three different diameters were inserted and stabilized in a 3.7-mm burr hole in the rabbit tibia. The purpose of the study was to investigate the interfacial reaction to screw- and cylinder-shaped implants, and to determine if there is a critical gap at the insertion between bone and implant that prevents direct cortical bone apposition on the implant. The study indicated that this critical gap approached zero.

Animals↗
PubMed1988

Characterization of the inhibitory effect of some antidepressant drugs on the outward transport of norepinephrine in the ischemic myocardium.

The noradrenergic amine carrier has an important role in mediating the local release of norepinephrine (NE) during myocardial ischemia. The effects of the antidepressant or putative antidepressant drugs desipramine, 2-hydroxy desipramine, nisoxetine, (S)-oxaprotiline and (R)-oxaprotiline with respect to this release mechanism were investigated in the isolated rat heart submitted to total stop-flow ischemia and subsequent reperfusion. During the reperfusion phase a massive efflux of NE was observed, which was reduced in a concentration-dependent manner in the presence of the antidepressant drugs. The potency (pIC50) of the antidepressants in inhibiting the ischemia-induced NE release varied between 9.16 (desipramine) and 6.17 [(R)-oxaprotiline]. On the other hand, lidocaine (10 microM) or clonidine (1 microM) did not reduce the magnitude of the NE efflux. No attenuation in NE efflux could be detected when desipramine (0.1 microM) was present only during the reperfusion period. During repeated periods (3 x 20 min) of ischemia, desipramine (0.1 microM) reduced markedly the loss of NE. In another experiment in the isolated guinea pig heart, desipramine (0.1 microM) was also found to attenuate the ischemia-induced mobilization of NE to the same significant extent as in the isolated perfused rat heart. Chronic treatment (3 weeks) of rats with desipramine as well as acute administration of desipramine to rats (2 hr before the initiation of perfusion) caused a pronounced reduction in the ischemia-induced release of NE in the isolated perfused heart. In conclusion, these experiments strongly suggest that a major part of the ischemia-induced release of NE is mediated by the amine carrier associated with the noradrenergic nerve terminal membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

A two-site monoclonal enzyme immunoassay for pregnancy-associated alpha 2-glycoprotein.

A two-site monoclonal enzyme immunoassay (MEIA) was developed for the determination of pregnancy-associated alpha 2-glycoprotein (PA alpha 2G) in serum. The minimum detectable level was 35 ng/ml. No immunochemical interaction with the closely related alpha 2-macroglobulin was found. Serum levels in 145 normal healthy males and non-pregnant females were 1.8 +/- 2.8 micrograms/ml (mean +/- SD), respectively, both significantly lower than previously reported. The distribution in the normal population was characteristically different when males and females were compared. No increase with age was found. During pregnancy, a significant increase in serum concentration was observed with average levels of 320 +/- 200 micrograms/ml at term (mean +/- SD), a 50-fold increase in concentration. As a tumor marker for breast and ovarian cancer, PA alpha 2G was found to be of no value. The present study emphasizes that a reevaluation of PA alpha 2G levels must be undertaken in order to assess the clinical and biological significance of this protein.

Antibodies, Monoclonal↗
PubMed1987

Early intraneuronal mobilization and deamination of noradrenaline during global ischemia in the isolated perfused rat heart.

Isolated rat hearts were perfused according to the Langendorff technique and both extraneuronal uptake of noradrenaline and COMT were inhibited. The noradrenergic neurones were first prelabelled with 3H-(-)-noradrenaline (13 nmol/l). Thereafter the hearts were submitted to global ischemia (perfusion rate reduced from 5 up to 0.5 ml/min) for 60 min and subsequently reperfused for 5 min. The coronary effluent was continuously collected and analyzed for the appearance of 3H-noradrenaline and its metabolites. 1. Global ischemia was associated with an early release of 3H-noradrenaline. At reperfusion a brisk increase in the FRL of 3H-noradrenaline was observed which may indicate that, on severe restriction in coronary flow, perfusion of the tissue became heterogenous and thus partially masked the amount of 3H-noradrenaline released from the noradrenergic nerve terminals. Gradual reduction in coronary flow also progressively reduced (but did not abolish) the total formation of 3H-DOPEG. 2. The maximal efflux of 3H-noradrenaline was observed during the 1st min of reperfusion whereafter the efflux declined rapidly, indicating a wash-out of transmitter trapped in the extracellular space. The efflux of the lipophilic metabolite 3H-DOPEG, on the other hand, continuously increased during the reperfusion. This was due to both new formation and "wash-out" of 3H-DOPEG retained and/or distributed into the tissue during the period of restricted flow. 3. Neither a reduction of the extracellular calcium concentration (from 2.6 mmol/l to 0.1 mmol/l) nor the presence of the calcium entry blocker verapamil (250 nmol/l) reduced the efflux of 3H-noradrenaline seen during ischemia and reperfusion. 4. Desipramine (100 nmol/l) markedly reduced the ischemia-induced release of 3H-noradrenaline and simultaneously attenuated the formation of 3H-DOPEG. 5. A moderate reduction in the ischemia-induced mobilization of 3H-noradrenaline was seen in hearts perfused with 1 mumol/l reserpine, whereas the formation of 3H-DOPEG from such hearts was markedly higher than in corresponding controls. Only minor deviations from this pattern was observed when desipramine was present in addition to reserpine. It is concluded that a severe restriction in myocardial perfusion rate is associated with an enhanced net leakage of vesicular noradrenaline. This results in a rise of the free axoplasmic noradrenaline concentration which, in combination with an altered transmembrane sodium gradient, induces an increased local release of noradrenaline partly mediated by a calcium-independent, carrier-mediated outward transport.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Oestradiol increases baseline growth hormone levels in the male rat: possible direct action on the pituitary.

The effect of oestradiol treatment on the secretion of growth hormone (GH) was investigated in normal unrestrained male rats with chronic i.v. cannulae and in hypophysectomized male rats with autotransplanted pituitaries. The effect of gonadectomy of normal rats on the plasma GH secretory pattern was also evaluated. Baseline plasma GH levels were elevated following estradiol treatment of normal male rats (1.5 mg kg-1 per 15 days). Gonadectomy of male rats also resulted in increased baseline GH levels, although the effect was less apparent than after oestradiol administration. The pulse height was not influenced by gonadectomy or oestradiol administration. In male rats with the pituitary autotransplanted to the kidney capsule, oestradiol caused a dose-dependent increase in plasma GH levels, while there was no such effect of testosterone. These results suggest that the stimulatory influence of oestradiol on baseline GH levels is, at least partly, due to a direct effect on the pituitary. Plasma prolactin levels were elevated in rats with pituitary transplants receiving oestradiol. It is concluded that oestrogen administration to normal male rats increases baseline plasma GH levels, possibly by an effect exerted directly at the pituitary level.

Animals↗
PubMed1987

Ischaemia-induced release of noradrenaline and creatine kinase in the isolated, working rat heart.

In order to examine an early ischaemia-induced local release of myocardial noradrenaline (NA), the left coronary artery of the isolated working rat heart was ligated for periods varying between 7.5 min and 30 min, followed by reperfusion for 5 min. As perfusion substrate, glucose, lactate or both were used. In part of the experiments, hearts were pre-labelled with [3H]NA. Already after 7.5 min of ischaemia, an increased efflux of endogenous NA was observed in the perfusate at reperfusion, concomitant with a decrease in tissue NA content. This effect was most pronounced with lactate as substrate. Qualitatively similar effects were seen on [3H]NA efflux from labelled hearts. The combination of glucose and lactate as substrate markedly reduced (compared with lactate alone) the efflux of NA, whereas no such reduction was observed on the efflux of creatine kinase (CK). It is concluded that ischaemia is associated with an early local release of NA. Furthermore, ischaemia may induce different effects on the metabolic processes of the myocyte as compared with the adrenergic nerve ending.

Animals↗
PubMed1987

Differential effects of growth hormone and insulin-like growth factor I on colony formation of epiphyseal chondrocytes in suspension culture in rats of different ages.

The effect of human GH (hGH) and insulin-like growth factor I (IGF-I) on the colony formation of rat epiphyseal chondrocytes was studied in suspension culture. Chondrocytes from epiphyseal growth plates of the proximal tibia of 7-, 20-, and 28-day-old normal male rats were enzymatically isolated and cultured in the presence of 10% newborn calf serum in suspension stabilized with 0.5% agarose. The cloning efficiency (number of formed colonies per 1000 seeded cells) was 13.7 +/- 1.9, 3.2 +/- 0.6, and 3.5 +/- 0.4 for chondrocytes isolated from 7-, 20- and 28-day-old rats and cultured for 14 days, respectively. The colonies were classified according to size (colony diameter), and the number of colonies was estimated as a function of colony size (distribution of cloning efficiency). IGF-I (25-200 ng/ml) increased the total colony number among chondrocytes isolated from the three different age groups and particularly increased the number of small colonies. However, IGF-I did not significantly change the distribution of cloning efficiency as compared to the control group. hGH potentiated colony formation at concentrations of 10-80 ng/ml, but no stimulatory effect of hGH was apparent at a concentration of 160 ng/ml. GH caused an assymetric distribution of cloning efficiency that was significantly different from the control group due to an increased number of large colonies (diameter exceeding 80 microns). The differential effects of GH and IGF-I were apparent after an extended period of culture (28 days) at various concentrations of the peptides. These results show that GH as well as IGF-I induced colony formation among epiphyseal chondrocytes in suspension culture, although the effects of GH and IGF-I are different in terms of distribution of cloning efficiency. The observation that GH particularly potentiated the formation of large size colonies suggests that GH promotes the differentiation of prechondrocytes, or young chondrocytes as suggested earlier. The finding that IGF-I stimulation resulted in a higher proportion of small size chondrocyte colonies, compared to the control group, suggests that IGF-I stimulates epiphyseal chondrocytes at a later stage of differentiation.

Aging↗
PubMed1987

An experimental model for pharmacokinetic studies of monoclonal antibodies in human colonic cancer.

An experimental model consisting of athymic rats carrying human colonic tumours from cell line LS 174T in both hind legs was used. 125I-labelled anti-carcinoembryonic antigen (anti-CEA) monoclonal antibodies were injected intra-arterially (i.a.), either alone (21 rats) or together with degradable starch microspheres (6 rats). As a control, an irrelevant antibody was injected i.a., alone (6 rats) or together with microspheres (3 rats). An intra-arterial injection was given on the side bearing one tumour in each rat, while the contralateral tumour served as an 'intravenous' control. The rats were submitted to external gamma measurements daily for four days. On the fourth day they were killed and pieces from the tumours and from various organs were examined by in vitro measurements. The results indicate strong expression of CEA in LS 174T cells grafted to athymic rats. No lasting enhancement of the tumour uptake was achieved by intra-arterial injection of antibodies as compared with the control tumours.

Animals↗
PubMed1987

Enhanced uptake of intra-arterially injected anti-CEA monoclonal antibodies in human colonic cancer after mannitol infusion in an experimental model.

In a previous report athymic rats carrying transplanted human colonic tumours from cell line LS 174T in both hind legs were injected intra-arterially (i.a.) with 125I-labelled anti-carcinoembryonic (anti-CEA) monoclonal antibodies. The i.a. injection was given on one side bearing a tumour in each rat, while the contralateral tumour served as an 'intravenous' control. In the same experimental model and treated in the same way, 10 rats were injected i.a. with anti-CEA monoclonal antibodies after an i.a. mannitol infusion. In both groups of rats external gamma measurements were performed daily for four days. On the fourth day the rats were killed and pieces of the tumours and of various organs were weighed and the activity was determined with a gamma-counter. The tumour uptake of antibodies was significantly enhanced after mannitol infusion.

Animals↗