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S Karlsson

Publications and source records attributed to S Karlsson.

At least 199 records · Page 11Linked to original sources

Contribution of galanin to stress-induced impairment of insulin secretion in swimming mice.

This study examines the potential role of the neuropeptide, galanin, in stress-induced inhibition of insulin secretion in swimming mice. Firstly, the pancreatic and adrenal content of galanin-like immunoreactivity was determined in mice after swimming stress. It was found that pancreatic content was significantly lower in stressed mice than in resting controls, both after 2 (P less than 0.05) and 6 (P less than 0.025) minutes of swimming, suggesting partial release of pancreatic galanin during stress. In contrast, the adrenal content of galanin-like immunoreactivity did not change during the swimming stress. Gel filtration of tissue extracts indicated that (1) mouse pancreas contains two forms of galanin-like immunoreactivity; one co-eluting with synthetic porcine galanin (centered on Kav of 0.70) and another with a larger molecular weight (centered on Kav of 0.30), and (2) mouse adrenal contains a small void volume-peak and a larger peak of immunoreactivity, the latter co-eluting with synthetic galanin. Secondly, the effects of swimming stress on plasma glucose and insulin levels were compared in mice that received high titre rabbit anti-galanin serum with those in mice receiving normal rabbit serum. In normal rabbit serum-pretreated swimming mice, glucose-induced insulin levels were only 50% of resting controls (P less than 0.01). Immunoneutralization of galanin with specific antiserum abolished this swimming stress-induced inhibition of glucose-stimulated insulin levels. This was accompanied by a modestly enhanced rate of glucose disappearance. These findings suggest that pancreatic galanin is released during swimming stress in mice and that endogenous galanin makes a major contribution to stress-induced impairment of insulin secretion.

Adrenal Glands↗

Characteristics of masticatory mandibular movements and velocity in growing individuals and young adults.

Studies of the development of mastication in the normal growing individual have received little attention in the literature. The aim of this study was to determine whether changes in oral motor function occurred during growth. Ninety healthy individuals with normal occlusion were divided into six groups of males and females, 9-10, 13-15, and 20-22 years of age. Oral motor function, with respect to mandibular displacement and velocity, was monitored with an opto-electronic method. The results revealed that the total duration of the masticatory cycle was not influenced by age or gender. However, the time distribution between the different phases was found to be influenced by the age factor, causing a longer opening time and a shorter closing time in the adults. In mastication, both mandibular displacement and the mandibular velocity in closing were less in females. A reduction of the masticatory opening velocity and an increase in closing velocity were observed with increasing age. Physiological maturation of the masticatory system due to central and peripheral changes and functional adjustments due to changes in dentition and skeletal growth may be the underlying reasons for our findings.

Adolescent↗

Dependence on extracellular Ca2+ for the effects of cholecystokinin-8 in rat pancreatic islets.

The dependence on extracellular Ca2+ for the insulinotropic effect of cholecystokinin-8 (CCK-8) and CCK-8-induced cellular events in isolated rat islets was investigated. CCK-8 stimulated insulin secretion at 8.3 mM glucose in the presence but not in the absence of extracellular Ca2+. In contrast, efflux of 45Ca2+ from 45Ca(2+)-prelabelled islets was stimulated by CCK-8 to the same extent in the presence as in the absence of extracellular Ca2+. This shows that CCK-8 mobilizes intracellularly stored Ca2+. CCK-8 also stimulated 3H-efflux from myo-[2-3H]inositol-prelabelled islets showing that the peptide activates phosphoinositide (PI) hydrolysis. The PI-hydrolysis persisted, but was reduced, in the absence of extracellular Ca2+. This suggests that PI-hydrolysis might underly the liberation of intracellularly stored Ca2+ induced by CCK-8. CCK-8 also stimulated 86Rb(+)-efflux (reflecting K(+)-movements) from 86Rb(+)-prelabelled islets. This effect was clearly reduced, but not absent, in a Ca(2+)-deficient medium, suggesting opening of Ca(2+)-dependent K(+)-channels. Our results show that although CCK-8 mobilizes intracellularly stored Ca2+ and stimulates PI-hydrolysis also in the absence of extracellular Ca2+, the insulinotropic effect of CCK-8 requires the presence of extracellular Ca2+.

Analysis of Variance↗

Adaptive changes of masticatory movement characteristics after rehabilitation with osseointegrated fixed prostheses in the edentulous jaw: a 10-year follow-up study.

The aim of this study was to assess possible adaptive changes in the masticatory rhythmical pattern after insertion of an osseointegrated fixed denture. Registrations of masticatory cycle duration, mandibular velocity, and displacement were performed before and 2 months and 10 years after rehabilitation. No major changes except for a decreased occlusal level phase had occurred regarding cycle duration over the years. However, a significantly higher mandibular velocity and greater displacement were recorded 2 months after rehabilitation. This trend was further established in the long term. Temporal timing of rhythmical chewing seems to be relatively consistent, suggesting that the central pattern generator driving output over time is constant.

Adaptation, Physiological↗

Peptide receptor antagonists in the study of insulin and glucagon secretion in mice.

Peptide antagonists might be useful tools in elucidating a potential role for neuropeptides in islet hormone secretion. We therefore investigated the effects of three different peptide receptor antagonists on insulin and glucagon secretion in vivo in mice. The gastrin-releasing peptide (GRP) antagonist N-acetyl GRP-(20-26) amide (P less than 0.01) and the vasoactive intestinal polypeptide (VIP) antagonist [4Cl-D-Phe 6,Leu17] VIP (P less than 0.001) specifically inhibited insulin secretion induced by GRP and VIP, respectively. Furthermore, N-acetyl GRP-(20-26) amide specifically inhibited GRP-stimulated glucagon secretion (P less than 0.01) and the cholecystokinin (CCK) antagonist L-364,718 inhibited CCK-8-mediated insulin and glucagon secretion (P less than 0.001). However, neither of these three antagonists affected insulin or glucagon secretion stimulated by autonomic nerve activation (induced by 2-deoxy-glucose (2-DG)). We conclude that these peptide antagonists can be used in studies on the physiological involvement of GRP, VIP and CCK in islet hormone secretion. Furthermore, neither GRP or CCK seems involved in the insulin and glucagon response to 2-DG in the mouse.

Animals↗

Effects of porcine diazepam-binding inhibitor on insulin and glucagon secretion in vitro from the rat endocrine pancreas.

Porcine diazepam-binding inhibitor (pDBI) is a novel peptide that has been isolated from the small bowel of the pig, and that occurs also in the islet D-cells. We have studied its effects on hormone release in vitro from the endocrine pancreas of the rat. In isolated islets, pDBI (10(-9)-10(-6)M) did not affect basal insulin release at 3.3 mM glucose, whereas stimulated release at 8.3 mM glucose was dose-dependently suppressed by 32-69% (P less than 0.01). Furthermore, insulin secretion stimulated by either 16.7 mM glucose or 1 mM IBMX (3-isobutyl-1-methylxanthine) or 1 micrograms/ml glibenclamide was suppressed by pDBI at 10(-8) M (by 28-30%, P less than 0.05) and 10(-7) M (by 43-47%, P less than 0.01). In contrast, islet insulin secretion induced by 20 mM arginine was unaffected by these concentrations of pDBI. In the perfused rat pancreas, pDBI (10(-8) M) enhanced by 30% (P less than 0.05) the first phase (0-5 min) of arginine-stimulated insulin release, whereas the second phase (5-20 min) was unchanged. Moreover, pDBI suppressed by 28% (P less than 0.05) the second phase of arginine-induced glucagon release. Arginine-induced somatostatin release was not significantly affected by the peptide. Since pDBI immunoreactivity has been localized also to islet D-cells, the present results suggest that pDBI may act as a local modulator of islet hormone release.

1-Methyl-3-isobutylxanthine↗

Insulin and glucagon secretion in swimming mice: effects of autonomic receptor antagonism.

To study the regulation of islet hormone secretion in exercise-stress, we developed a swimming mouse model. Mice swam for 2, 6, or 10 minutes whereafter blood was sampled for analysis of plasma levels of insulin, glucagon, and glucose. Plasma insulin levels, which were not different from resting controls after 2 or 6 minutes of swimming, were slightly lower after 10 minutes of swimming (P less than .05). Plasma glucagon levels were increased after 2, 6, and 10 minutes of swimming (P less than .001), and plasma glucose levels were lower after 6 and 10 minutes of swimming (P less than .05). Glucose (5.6 mmol/kg)-stimulated insulin secretion was inhibited by 52% +/- 9% by the swimming (P less than .001). The mechanisms behind this inhibition of glucose-stimulated insulin secretion and the increase in basal plasma glucagon levels induced during 2 minutes of swimming were investigated by the use of autonomic receptor antagonists, administered intraperitoneally 20 minutes before the swimming period. The ganglionic antagonist hexamethonium (56 mumols/kg) prevented the swimming-induced inhibition of glucose-stimulated insulin secretion, indicating involvement of nerves in the inhibition. Also the nonselective alpha-adrenoceptor antagonist phentolamine (6.0 mumols/kg) and the alpha 2-adrenoceptor antagonist yohimbine (3.6 mumols/kg) prevented the inhibition of glucose-stimulated insulin secretion induced by swimming, whereas the beta-adrenoceptor antagonist L-propranolol (9.6 mumols/kg) had no effect. The swimming-induced increase in plasma glucagon levels was partially inhibited by hexamethonium by (58% +/- 24%, P less than .05). Phentolamine and yohimbine totally prevented the increase in plasma glucagon levels, whereas L-propranolol had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Correction of glucocerebrosidase deficiency after retroviral-mediated gene transfer into hematopoietic progenitor cells from patients with Gaucher disease.

Retroviral gene transfer has been used successfully to correct the glucocerebrosidase (GCase) deficiency in primary hematopoietic cells from patients with Gaucher disease. For this model of somatic gene therapy, we developed a high-titer, amphotropic retroviral vector designated NTG in which the human GCase gene was driven by the mutant polyoma virus enhancer/herpesvirus thymidine kinase gene (tk) promoter (Py+/Htk). NTG normalized GCase activity in transduced Gaucher fibroblasts and efficiently infected human monocytic and erythroleukemic cell lines. RNA blot-hybridization (Northern blot) analysis of these hematopoietic cell lines showed unexpectedly high-level expression from the Moloney murine leukemia virus long terminal repeat (Mo-MLV LTR) and levels of Py+/Htk enhancer/promoter-initiated human GCase RNA that approximated endogenous GCase RNA levels. Furthermore, NTG efficiently infected human hematopoietic progenitor cells. Detection (by means of the polymerase chain reaction) of the provirus in approximately one-third of NTG-infected progenitor colonies that had not been selected in G418-containing medium indicates that relative resistance to G418 underestimated the actual gene transfer efficiency. Northern blot analysis of NTG-infected, progenitor-derived cells showed expression from both the Mo-MLV LTR and the Py+/Htk enhancer/promoter. NTG-transduced hematopoietic progenitor cells from patients with Gaucher disease generated progeny in which GCase activity had been normalized.

Blotting, Northern↗

Expression of human glucocerebrosidase in long-term reconstituted mice following retroviral-mediated gene transfer into hematopoietic stem cells.

A retroviral vector (GTN) in which the glucocerebrosidase (GCase) cDNA is driven by the Moloney murine leukemia virus (Mo-MuLV) long terminal repeat (LTR) was tested for transfer efficiency and expression of the GCase gene in long-term reconstituted mice. Eleven W/Wv mice were transplanted with unselected GTN-infected bone marrow cells and 10 of these mice were analyzed 3 months later. Seven of these 10 mice (70%) contained the intact proviral genome in bone marrow, spleen, and thymus. Of these 7,3 mice contained a high-copy number of the provirus in all the hematopoietic tissues tested. The mice contained anywhere from one to four proviral integration sites that were the same in all three tissues, indicating that these mice have been repopulated by one or more transduced multipotential hematopoietic stem cells. Five months after transplantation, bone marrow from the eleventh mouse was transplanted into secondary recipient animals. The secondary recipients contained the intact proviral genome in the bone marrow, spleen, thymus, and macrophages 4 months after the secondary transplantation. This further supports the conclusion that hematopoietic stem cells have indeed been targeted. Human GCase RNA was detected in all 7 mice containing the proviral DNA. These results demonstrate expression of the human GCase gene in the progeny of repopulating hematopoietic stem cells of mice following gene transfer.

Animals↗

Characteristics of mandibular masticatory movement in young and elderly dentate subjects.

Dimensions and velocity of mandibular movement are important variables in the evaluation of masticatory and speech patterns. However, little information is available concerning elderly dentates and their oral motor function and behavior. Double recordings of a chewing period, from start to swallowing, were performed in 14 elderly (mean age, 80 years) and 30 young (mean age, 26 years) dentate subjects chewing crispbread. Three-dimensional records of mandibular movements were obtained by means of the Selspot movement analysis system, which monitors infrared light pulses from light-emitting diodes attached to the test subject. There was no difference in the duration of the total chewing cycle between the two groups. Mandibular velocity was significantly lower in the elderly group, in both the opening and the closing phases. Despite great inter-individual variations, significantly smaller mean vertical displacements of the mandible were found in the elderly than in the younger group. The lateral component in the vertical opening movement was similar for both the elderly and younger subjects. The similar chewing rates in the two groups might imply that the function of the central pattern generator was unaffected by old age. Aging was, however, associated with reduction of vertical mandibular displacement and velocity.

Adult↗

Effect of a denture adhesive on mandibular denture dislodgment.

The cineradiographic technique was used to assess the retention of complete mandibular dentures during chewing. The study comprised ten complete-denture wearers with severe alveolar ridge resorption in the mandible. Two cineradiographic recordings were performed, with and without a denture adhesive spread onto the base of the mandibular denture. The analysis of the cineradiographic films disclosed a significant decrease in denture dislodgment, expressed as maximal value, when a denture adhesive was used. The mean dislodgment also decreased, but not significantly.

Adhesives↗

Combination of interleukins 3 and 6 preserves stem cell function in culture and enhances retrovirus-mediated gene transfer into hematopoietic stem cells.

The effects of several hematopoietic growth factors on primitive murine bone marrow progenitor cells [colony-forming unit(s)-spleen (CFU-S)] have been investigated during culture for 2-6 days. Interleukin 3 (IL-3) was required for CFU-S survival in culture, and the combination of IL-3 and interleukin 6 (IL-6) increased the number of CFU-S in culture 10-fold over the number obtained with IL-3 alone. Stem cell function was measured by competitive repopulation; IL-3 was required, and IL-3 and IL-6 appear to act synergistically to enhance stem cell recovery from these cultures. These data appear to be relevant for retroviral-mediated gene transfer into stem and progenitor cells. Murine bone marrow cells were infected with a retrovirus containing the human beta-globin gene in the presence of various growth factors. Only 2 of 17 mice reconstituted with cells infected in the presence of IL-3 alone showed long-term expression of the human beta-globin gene (12 months), as opposed to 6 of 11 mice reconstituted with cells infected in the presence of IL-3 and IL-6. Medium conditioned by 5637 bladder carcinoma cells, a source of several hematopoietic growth factors, increased the frequency of infection of CFU-S but did not enhance stem cell infection or the repopulating potential of cultured bone marrow cells. Stem cells containing the human beta-globin provirus from these animals were shown to be capable of reconstituting secondary recipients in which the human beta-globin gene was expressed.

Animals↗

Production of human glucocerebrosidase in mice after retroviral gene transfer into multipotential hematopoietic progenitor cells.

The human glucocerebrosidase (GC) gene has been transferred efficiently into spleen colony-forming unit (CFU-S) multipotential hematopoietic progenitor cells, and production of human GC RNA and protein has been achieved in transduced CFU-S colonies. High-titer retroviral vectors containing the human GC cDNA were constructed. Mouse bone marrow cells were stimulated with hematopoietic growth factors, infected by coculture with producer cells, and injected into lethally irradiated animals. Four vectors were compared with respect to gene-transfer efficiency into CFU-S progenitors. One vector (G vector) required high concentrations of interleukins 3 and 6 during stimulation and coculture for efficient transduction of CFU-S progenitors. The remaining three vectors (NTG, GTN, and GI vectors) transduced these progenitors at infection frequencies approaching 100% using low concentrations of hematopoietic growth factors to stimulate cell division prior to and during the infection. Vectors using the viral long terminal repeat enhancer/promoter to drive the human GC cDNA produced high levels of human GC RNA in the progeny of CFU-S progenitors after gene transfer. When an internal herpes simplex thymidine kinase promoter assisted by a mutant polyoma enhancer was used to drive the human GC cDNA (NTG vector), little or no human GC RNA was detected in transduced CFU-S colonies. All three vectors producing human GC RNA in CFU-S colonies can generate human GC as detected by immunochemical analysis of CFU-S colonies. NTG vector-infected bone marrow cells were transplanted into W/Wv recipients to generate long-term reconstituted mice. The capacity of the viral long terminal repeat and the internal thymidine kinase promoter to direct synthesis of RNA in transduced bone marrow and spleen cells 5 months after bone marrow transplantation reflected the performance of these promoters in NTG-transduced CFU-S colonies.

Animals↗

Cinefluoroscopic study of long-term changes of bolus position and chewing cycle duration after fixed prosthetic treatment.

Some chewing parameters were studied in 12 patients with a complete maxillary denture and a 12-unit fixed mandibular denture anchored to the two canines. Registration by means of fluoroscopy were made before, 1 month after, and in four patients 13 yr after treatment. The mean velocity of the mandible during chewing increased after the prosthetic treatment and remained stable for meat during the observation period. At the first registration, before treatment, the bolus was most frequently located in the anterior region. After completion of the prosthetic rehabilitation, the bolus was mainly located to the lateral segments during chewing of the test foods, namely meat and bread. The recordings were almost identical 13 yr later. Despite a very reduced periodontal support, posterior cantilevered segments were satisfactorily used in comminution and the patients seemed to be unaware of the forces exerted on the remaining teeth.

Adult↗

Effects of three different cholecystokinin receptor antagonists on basal and stimulated insulin and glucagon secretion in mice.

Cholecystokinin (CCK) receptor antagonists may be valuable tools for investigating the physiological role of CCK in islet function. In this study, the effects of the three different CCK receptor antagonists, proglumide, CR 1409 and L-364,718, on basal and stimulated insulin and glucagon secretion were investigated in vivo in the mouse. Each of the CCK antagonists was injected intravenously, either alone or together with one of the secretagogues CCK-8 (5.3 nmol kg-1), carbachol (0.16 mumol kg-1) or glucose (2.8 mmol kg-1). At a low dose level, proglumide (28 mumol kg-1) inhibited selectively CCK-8-induced insulin and glucagon secretion. However, at a higher dose level (280 mumol kg-1), proglumide inhibited also carbachol- and glucose-induced insulin secretion. Furthermore, proglumide elevated basal plasma levels of both glucagon and glucose. CR 1409 inhibited CCK-8-induced insulin secretion at a high (21 mumol kg-1) but not at a low (0.21 mumol kg-1) dose level. In contrast, CCK-8-induced glucagon secretion was not affected by CR 1409. L-364,718 (2.4 mumol kg-1) inhibited both CCK-8-induced insulin and glucagon secretion. In contrast, L-364,718 did not affect basal plasma levels of insulin, glucagon or glucose or those levels after stimulation with carbachol or glucose. We conclude that, of these three CCK antagonists, L-364,718 is the most specific CCK receptor antagonist for studies of both insulin and glucagon secretion in the mouse.

Animals↗

Three cases of neonatal meningitis caused by Enterobacter sakazakii in powdered milk.

Three cases of neonatal infection caused by Enterobacter sakazakii are reported from the Department of Neonatal Intensive Care, the National University Hospital, Reykjavík, Iceland. These infections occurred during a 9-month period in 1986 and 1987. Two of the neonates, who were normal at birth, survived but were left with brain damage. The third, who had Down's syndrome and severe cardiac malformations, died. The same organism was also grown from groin and anal swabs from a healthy neonate. E. sakazakii was not isolated from any environmental sources in the neonatal wards or in the milk kitchen, but it was grown from several lots of the powdered-milk formula used in the hospital. The four E. sakazakii strains isolated from the neonates were indistinguishable from 22 strains grown from the formula. Their biotypes, plasmid DNA profiles, and antibiograms were identical.

Animals↗