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E Karlsson

Publications and source records attributed to E Karlsson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Insulin-like growth factor I response during nutritional rehabilitation of persistent diarrhoea.

OBJECTIVE: Evaluation of nutritional recovery, intestinal permeability, and insulin-like growth factor I (IGF-I) response in malnourished children with persistent diarrhoea and their relation to concomitant systemic infection(s). STUDY DESIGN: Open study of severely malnourished children (aged 6-36 months) with persistent diarrhoea (>/= 14 days) admitted for nutritional rehabilitation with a standardised rice-lentil and yogurt diet. Successful recovery was defined prospectively as overall weight gain (> 5 g/kg/day) with a reduction in stool output by day 7 of treatment. Data on coexisting infections and serum C reactive protein (CRP) were collected at admission. RESULTS: Of 63 children, 48 (group A) recovered within seven days of dietary treatment. These children had a significant increase in serum IGF-I (DeltaIGF-I%) and, in contrast to serum prealbumin and retinol binding protein, DeltaIGF-I% correlated with weight gain (r = 0.41). There was no correlation between the IGF-I response and intestinal permeability as assessed by urinary lactulose/rhamnose excretion. Treatment failures (group B) included more children with clinical (relative risk, 4.8; 95% confidence interval, 1.2 to 19.7) and culture proven sepsis at admission and higher concentrations of serum CRP (median (range), 36 (0-182) v 10 (0-240) mg/l) at admission. There was a negative correlation between admission CRP concentration and DeltaIGF-I% (r = -0.45). CONCLUSIONS: In comparison with serum albumin, prealbumin, and retinol binding protein, serum IGF-I increment is a better marker of nutritional recovery in malnourished children with persistent diarrhoea. The possible association of systemic infections, serum IGF-I response, and mucosal recovery needs evaluation in future studies.

Biomarkers↗
PubMed1999

IAPP as a regulator of glucose homeostasis and pancreatic hormone secretion (review).

IAPP is a 37-amino acid peptide that is predominantly expressed in pancreatic beta cells. Despite co-secretion from islets the relative amounts of IAPP and insulin may vary. Since IAPP was first described as the major peptide constituent of amyloid in the islets of Langerhans of subjects with type 2 diabetes and insulinoma, many studies have been devoted to investigating the role of IAPP in formation of amyloid deposits and in diabetes pathogenesis. However, there is growing evidence for IAPP as an active islet hormone in addition to insulin and glucagon in glucose metabolic control. An inhibitory effect is seen by IAPP on gastric emptying, glycogen synthesis in skeletal muscle, islet insulin and glucagon secretion, whereas a stimulatory effect is seen on hepatic gluconeogenesis.

Amino Acid Sequence↗
PubMed1999

Selectivity profile of muscarinic toxin 3 in functional assays of cloned and native receptors.

By using acetylcholine-induced stimulation of [35S]guanosine-5'-O-(3-thio)triphosphate ([35S]GTPgammaS) binding to membrane G proteins as a functional assay of the cloned human m1-m4 muscarinic receptor subtypes stably expressed in Chinese hamster ovary cells, muscarinic toxin 3 (MT3) was found to block the m4 receptor with a potency (pA2 = 8.33) much higher than those displayed at the m1 (pA2 = 6.78), m3 (pA2 = 6.3), and m2 (pA2 < 6.3) subtypes. In N1E-115 cells, which have been reported to express m4 receptors coupled to inhibition of cAMP, MT3 potently antagonized the carbachol-induced inhibition of adenylyl cyclase with a pA2 of 8. 81 and displayed monophasic inhibitory curves. Unexpectedly, in NG108-15 cells, known to express only m4 receptors, MT3 counteracted the carbachol inhibition of adenylyl cyclase with a lower potency (pA2 = 7.60) and showed a biphasic inhibitory curve, suggesting the participation of both m4 and m2 receptors. This possibility was supported by radioligand binding data showing that MT3 failed to completely displace the binding of [3H]N-methylscopolamine to NG108-15 cell membranes and by reverse transcription-polymerase chain reaction analysis, revealing the presence of mRNAs for both m4 and m2 receptor subtypes. These data demonstrate that MT3 possesses a high functional receptor selectivity for both the cloned and native m4 receptors and that in cell systems containing m4 and m2 receptors coupled to a common response, the toxin constitutes a powerful tool to resolve the relative contribution by each receptor subtype.

Adenylyl Cyclases↗
PubMed1998

Discrimination of human tumor radioresponsiveness using low-dose rate irradiation.

PURPOSE: Evaluation of the theoretical and practical value of using low-dose rate (LDR) irradiation to increase the resolution of radiosensitivity testing of primary human tumors using clonogenic assays. METHODS AND MATERIALS: Fourteen human tumor cell lines were assessed for surviving fraction at 2-8 Gy (SF2-SF8) using low-dose rate irradiation and a clonogenic assay. Further data were collected from the literature for 64 low-dose rate irradiation survival curves from human tumor cell lines. The data were grouped into five different radioresponsiveness categories (A-E). An analysis was made of the ability of the graded survival levels to discriminate between the different radioresponse groups and compared with previous analyses for high-dose rate SF2. Fifteen human cervical carcinoma specimens were analysed for SF2 and SF3.5 following high- and low-dose rate irradiation. RESULTS: Low-dose rate irradiation increased the spread of tumor cell line radiosensitivity data and the ability to discriminate between radioresponse groups was greater at low than at high-dose rates. Using low-dose rate irradiation on primary tumor specimens and a soft agar clonogenic assay decreased the success rate in obtaining data. The latter dropped from 70% for high-dose rate SF2 to 51% for low-dose rate SF3.5. CONCLUSIONS: The work on cell lines illustrates that low-dose rate irradiation does improve the ability of clonogenic radiosensitivity measurements to discriminate between tumors of different radioresponsiveness groups. However, using low-dose rate irradiation on primary human tumors with a soft agar clonogenic assay was not practical because of reducing the success rate for obtaining data for radiosensitivity measurements.

Cell Survival↗
PubMed1998

Leptin regulation of islet amyloid polypeptide secretion from mouse pancreatic islets.

Leptin receptors are expressed in pancreatic beta-cells. However, leptin's role in islet hormone secretion is essentially unknown. In the present study, we aimed to elucidate leptin's effect on isolated pancreatic NMRI mouse islets by examining islet amyloid polypeptide (IAPP) and insulin secretion in acute experiments and after 48-hr exposure to leptin (1-100 nM). It was also examined whether a putative effect of leptin was affected by the glucose concentration. Islets were cultured in medium RPMI 1640 + 10% fetal calf serum, and the effects of leptin on islet cell replication, glucose metabolism, and hormone content were subsequently examined. Glucose-stimulated IAPP secretion was reduced both acutely and after 48-hr exposure to leptin, whereas only minor effects were found on insulin release, i.e. an inhibition in islets cultured with 1 nM leptin. An acute inhibitory effect by 10 nM leptin was observed on the ratio of IAPP/insulin release at 5.6-11.1 mM glucose, but this was overcome by 16.7 mM glucose. The islet glucose oxidation rate was enhanced by 1 nM leptin, but decreased at higher concentrations of leptin in acute experiments. In contrast, glucose metabolism was not affected in long-term experiments. Moreover, leptin did not influence islet (pro)insulin synthesis or the cell replication rate after culture. In conclusion, we show that islet IAPP release seems to be more sensitive to leptin than is insulin release. The effect of leptin on islet hormone secretion is dependent on the glucose concentration. The regulation of hormone secretion seems to be dissociated from glucose metabolism, an effect previously described in islets after exposure to certain cytokines. Our data necessarily suggest that a previously proposed negative feedback loop between leptin and insulin can be counteracted by IAPP.

Amyloid↗
PubMed1998

Identification of rat brain muscarinic M4 receptors coupled to cyclic AMP using the selective antagonist muscarinic toxin 3.

In membranes of olfactory tubercle and striatum, the selective muscarinic M4 receptor antagonist muscarinic toxin 3 completely antagonized the acetylcholine-induced inhibition of forskolin- and dopamine D1 receptor-stimulated cyclic AMP formation with Ki values of 7 and 4 nM, respectively. In olfactory bulb, where acetylcholine stimulated basal adenylyl cyclase activity and inhibited forskolin-stimulated enzyme activity, muscarinic toxin 3 caused a partial antagonism of both acetylcholine effects with high potencies (Ki values = 4-6 nM). In frontal cortex, muscarinic toxin 3 counteracted the acetylcholine-induced potentiation of corticotropin-releasing hormone-stimulated cyclic AMP with a Ki of 58 nM, which is close to the toxin affinity for the muscarinic M1 receptor. In the same brain region, the acetylcholine inhibition of forskolin-stimulated enzyme activity was not affected by muscarinic toxin 3. In microdissected regions of the hippocampus, a significant portion (33-48%) of the acetylcholine inhibition of forskolin-stimulated adenylyl cyclase activity was blocked by muscarinic toxin 3 with Ki values (6-8 nM) consistent with the involvement of muscarinic M4 receptors. These data show that muscarinic toxin 3 discriminates between adenylyl cyclase-coupled muscarinic receptors and demonstrate the utility of the toxin in identifying the relative contribution by the muscarinic M4 receptor subtype.

Adenylyl Cyclases↗
PubMed1998

The in vitro radiosensitivity of human head and neck cancers.

A study was made of the intrinsic radiosensitivity of 140 biopsy and surgical specimens of malignant head and neck tumours of different histologies. Using a soft-agar clonogenic assay, the material was assessed for the ability to grow in culture (colony-forming efficiency; CFE) and inherent tumour radiosensitivity (surviving fraction at 2 Gy, SF2). The success rate for obtaining growth was 74% (104/140) with a mean CFE of 0.093% (median 0.031) and a range of 0.002-1.3%. SF2 was obtained for 88 of 140 specimens, representing a success rate of 63% with a mean SF2 of 0.48 (median 0.43) and a range of 0.10-1.00. There were no significant differences in radiosensitivity between different sites of the head and neck region. There were no significant relationships between SF2 and disease stage, nodal status, tumour grade, patient age, primary tumour growth pattern and CFE. The results were compared with those for other tumour types previously analysed with the same assay. The distribution of the SF2 values for the head and neck tumours was similar to that for 145 cervix carcinomas and there was no significant difference in mean radiosensitivity between the two tumour types. Also, there was no significant difference in radiosensitivity between head and neck tumours and either breast or colorectal cancers. However, a group of eight lymphomas was significantly more radiosensitive. These results confirm the feasibility of carrying out radiosensitivity measurements using a soft-agar clonogenic assay on head and neck tumours. In addition, the work has shown that radiosensitivity is independent of many clinical parameters and that the mean value is similar to that reported for cervix carcinomas.

Head and Neck Neoplasms↗
PubMed1997

A potassium-channel toxin from the sea anemone Bunodosoma granulifera, an inhibitor for Kv1 channels. Revision of the amino acid sequence, disulfide-bridge assignment, chemical synthesis, and biological activity.

The potassium channel toxin secreted by the sea anemone Bunodosoma granulifera (BgK) is a 37-amino-acid peptide containing three disulfide bridges. Because a synthetic peptide corresponding to the reported sequence of BgK was found not to fold properly, the sequence was determined again. The new sequence differed from the previous one in the C-terminal tetrapeptide, which contains two cysteines involved in disulfide bridging. The revised sequence is: V C R D W F K E T A C R H A K S L G N C R T S Q K Y R A N C A K T C E L C. The toxin BgK was synthesized according to the new sequence and folded successfully. Disulfide bridges were assigned by peptide mapping on both natural and synthetic forms to be between Cys2-Cys37, Cys11-Cys30 and Cys20-Cys34. The toxin contains a C-terminal free carboxylate as shown by comparing the native toxin with two synthetic peptides containing the C-terminus in either the carboxylate or carboxamido form. Synthetic BgK inhibits binding of 125I-alpha-dendrotoxin to rat brain synaptosomal membranes, similarly to natural BgK (nanomolar range). No activity was observed on maxi-K+ channels incorporated into planar lipid bilayers. The ability of BgK to block voltage-dependent K+ channels was determined from recordings of whole cell currents in Xenopus oocytes injected with cRNA encoding three cloned Kv1 channels (Kv1.1, Kv1.2, Kv1.3) and one Kv3 (Kv3.1) channel. The Shaker-related Kv1 channels are equally affected by BgK, while the Shaw-related channel Kv3.1 is insensitive up to 0.125 microM toxin. Indeed, half blockage of the current through the three Kv1 channels tested occurred in the same concentration range (Kd = 6 nM for Kv1.1, 15 nM for Kv1.2, 10 nM for Kv1.3). The specificity of BgK for the Shaker-related K+ channels indicates that BgK is able to discriminate a large group of neuronal Kv1 channels in situ. The sequence, the disulfide bridge pattern, the secondary structure and the biological activity of BgK demonstrated that the sea anemone toxins, i.e. BgK, ShK and Kaliseptine, constitute novel molecular probes useful for investigating K+ channel properties.

Amino Acid Sequence↗
PubMed1997

Muscarinic receptor subtype selective toxins.

The muscarinic acetylcholine receptors are monomeric proteins with seven hydrophobic, membrane spanning helices, and share a common evolutionary origin with the other members of the superfamily of membrane proteins known as seven-helix receptors. The amino acid sequences of five different muscarinic acetylcholine receptors, called m1, m2, m3, m4 and m5 have been determined. The five subtypes are expressed to different extent in different tissues. A large number of low molecular ligands for muscarinic receptors are known, but they bind to all five subtypes of receptors and only a few of them have a slightly higher (five-six fold) affinity for one of the subtypes, e.g. pirenzepine for M1 (1) and tripitramine for M2 receptors (2). Several neurotoxins have been isolated from snake venoms and used as pharmacological tools. Mambas, African snakes of genus Dendroaspis, have toxins that recognize muscrinic receptors and some of these muscarinic toxins are the most selective ligands for M1 and M4 receptors known to date.

Amino Acid Sequence↗
PubMed1997

Workshop: the use of muscarinic toxins in the study of muscarinic receptors.

One of the most interesting recent developments in the pharmacology of muscarinic receptors has been the finding of small proteins in the venoms of mamba snakes that bind with high affinity and selectivity to different subtypes of muscarinic receptors. In the workshop on muscarinic toxins, the practicalities of isolating, characterising and using these toxins as tools in the study of muscarinic receptors were discussed.

Animals↗
PubMed1997

Changes to biological activity following acetylation of dendrotoxin I from Dendroaspis polylepis (black mamba).

The potassium channel blocker dendrotoxin I was acetylated with acetic anhydride. Mono-acetyl derivatives of all seven lysine residues (N-terminus blocked) and a di-derivative were isolated by chromatography on the cation-exchanger Bio-Rex 70 and reversed-phase high-performance liquid chromatography. The derivative acetyl-Lys 29 and the di-derivative of Tyr 24 and Lys 28 had more than 1000 times lower affinity than the native toxin as determined by inhibition of the 125I-dendrotoxin binding to synaptosomal membranes from rat brain. Lys 29 is part of the triplet Lys-Lys-Lys (28-30) which also occurs in the homologous alpha-dendrotoxin where the triplet is not in the functional site, as shown by site-directed mutagenesis. Acetylation of Lys 29 may have produced large structural perturbations that inactivated the toxin. Acetylation of Lys 28 alone had little effect, but the toxin became almost inactive when both Lys 28 and Tyr 24 were modified. Ten experiments were conducted under similar conditions, but a derivative of Tyr 24 was obtained only three times. In these cases the toxin apparently had a different structure, with Tyr 24 accessible to the reagent. This may depend on freeze-drying, which can alter the structure of proteins. The third derivative with low activity was acetyl-Lys 5, with affinity decreased 20-fold. Lys 5 has a protruding side-chain that does not interact with any other group in the toxin molecule. Therefore, Lys 5 is probably part of the functional site for dendrotoxin's binding to the voltage-dependent K+ channels.

Acetic Anhydrides↗
PubMed1997

Localization of M1 muscarinic receptors in rat brain using selective muscarinic toxin-1.

Mambas, African snakes of the genus Dendroaspis, produce several types of toxins that are of pharmacological interest. The novel muscarinic toxin-1 (MT-1), from the green mamba Dendroaspis angusticeps, binds specifically to muscarinic M1 receptors in homogenates of rat cerebral cortex. Iodination of the toxin, 125I-muscarinic toxin-1 (125I-MT-1), renders the toxin selective for M1 muscarinic receptors. Quantitative measurement of 125I-MT-1 autoradiography in rat brain sections indicated highest labeling in the nucleus accumbens, striatum, and dentate gyrus. High densities of 125I-MT-1 binding sites were located in the CA1 region of the hippocampus, frontal, and parietal cortices. Moderate densities of binding sites were seen in temporal cortex, and hippocampal subregions CA2, CA3, and CA4, whereas low labeling was observed in the cerebellum and spinal cord.

Amino Acid Sequence↗
PubMed1997

Swedish nurses' estimation of fatigue as a symptom in cancer patients--report of a questionnaire.

Many studies show that chronic fatigue is the most frequently reported symptom related to cancer and its treatment. In order to evaluate the problem in Sweden, a questionnaire was mailed to 442 registered nurses in the autumn of 1995 with the aim of determining cancer nurses' views of the nature and causes of cancer-related fatigue and which, if any, nursing interventions they employed in the management of this problem. The response rate was 49%. The responses showed that these nurses regarded fatigue as the most common symptom in cancer patients, but there were few established nursing interventions. Also, nurses wanted further education and tools for evaluation of fatigue, its causes and treatment.

Attitude of Health Personnel↗
PubMed1997

More favourable haemodynamic effects from metoprolol than from captopril in patients with dilated cardiomyopathy.

AIM: The object of this study was to investigate and compare the haemodynamic effects of treatment with a beta receptor blocker (metoprolol) or an angiotensin-converting-enzyme inhibitor (captopril) in 54 patients with idiopathic dilated cardiomyopathy. METHOD: All patients had cardiac catheterization performed at rest and during exercise, before and after 3 months of treatment. RESULTS: The mean dose of metoprolol was 135 mg.day-1 and of captopril 98 mg.day-1. After treatment there was a significant reduction in left ventricular filling pressure both at rest (from 16 to 12 mmHg) and during exercise (from 27 to 20 mmHg) in the metoprolol group. In the captopril group a significant reduction was seen only during exercise (25 to 20 mmHg), compared to baseline. The stroke volume increased significantly after 3 months of therapy in the metoprolol group, both at rest (53 to 70 ml) and during exercise (56 to 79 ml). In the captopril group the increase reached significance only during exercise (72 to 79 ml). Cardiac output was maintained in both groups. CONCLUSION: There were positive effects on left ventricular function in the metoprolol group as well as in the captopril group. Metoprolol reduced left ventricular filling pressure at rest and increased stroke volume both at rest and during exercise significantly more than captopril.

Adrenergic beta-Antagonists↗
PubMed1996

Islet amyloid polypeptide (IAPP) secretion from pancreatic islets isolated from non-obese diabetic (NOD) mice.

The secretion of islet amyloid polypeptide (IAPP) during the course of insulin-dependent diabetes mellitus (IDDM) is essentially unknown. In the present study we elucidated this issue by examining IAPP and insulin secretion from isolated pancreatic islets obtained from IDDM-prone female NOD mice aged 6-9 weeks and 12-15 weeks and from non-IDDM-prone male NMRI mice. Basal islet hormone secretion at 1.7 mM glucose and after stimulation with 17 mM glucose or with 17 mM glucose + 5 mM theophylline was studied acutely or after 1 week of tissue culture. The levels of glucose-stimulated insulin release from NOD mouse islets increased after tissue culture, whereas it remained unchanged in NMRI mouse islets. Overall changes in islet insulin secretion were accompanied by similar changes in IAPP secretion. Acute after isolation, islets from NMRI mice displayed a reduced IAPP/insulin secretion ratio in response to the stimulation, which could reflect a destabilized hormone release. When the NOD mouse islets at 6-9 weeks of age were exposed to secretory stimuli the molar ratio of IAPP/insulin secretion declined. At a later stage of advanced insulitis (12-15 weeks) also the basal IAPP/insulin secretory ratio at low glucose tended to decline. If extrapolated to the early prediabetic phase of human IDDM, this would mean that a relative hypersecretion of insulin in relation to IAPP might occur, due to an increased secretory demand for insulin or due to an intrinsic change in the biology of the secretory cells.

Amyloid↗
PubMed1996

Fasciculin: modification of carboxyl groups and discussion of structure-activity relationship.

Norleucine methylester was coupled to carboxylates of fasciculin 2, a snake toxin that inhibits acetylcholinesterase (AChE). This neutralized negative charges but had no effect on the activity, suggesting that carboxyls do not participate in binding to AChE. Earlier results are discussed. Modification of three aromatic amino acids in the peripheral site of AChE, the binding site for fasciculin, decreased the affinity 100 to one million times. Neutralizing the charge of cationic groups of fasciculin lowered the affinity only three to seven times. A change in either the toxin or enzyme part of a binding site should have about the same effect. Since this was not so, it suggests that cationic groups of fasciculin do not bind to aromatic rings in the peripheral site.

Amino Acid Sequence↗