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Biomedical subjects

T Nilsson

Publications and source records attributed to T Nilsson.

At least 55 records · Page 3Linked to original sources

Protein sorting in the Golgi apparatus: a consequence of maturation and triggered sorting.

To explain how resident proteins distribute in peak-like patterns at various positions in the secretory pathway, Glick and co-workers postulated that resident proteins comprise different populations (termed kin populations) and that these compete with each other for entering retrograde transport carriers [Glick et al. (1997) FEBS Lett. 414, 177-181]. Using modelling and computer simulation, they could demonstrate that differences in competitiveness sufficed to generate overlapping but distinct peak-like steady state distributions of the different kin populations across the Golgi stack. In this study, we have tested the robustness of the competition model and find that over-expression or changes in the number of kin populations affect their overall steady state distributions. To increase the robustness of the system, we have introduced a milieu-induced trigger for recycling. This allows for a decrease in the coupling between kin populations permitting both over-expression as well as changes in the number of kin populations. We have also extended the model to include a Golgi to endoplasmic reticulum (ER) recycling pathway and find that only a small amount of resident proteins may recycle at any time without upsetting their observed distributions in the Golgi stack. The biological relevance of a trigger-induced sorting mechanism and ER recycling is discussed.

Binding, Competitive↗

[Atrial septal defect--catheter-based closure now feasible!].

Atrial septal defects (ASD) of hemodynamic significance are usually treated surgically in early childhood. However, many cases will not be detected until the patient has become an adult. As there is a risk of development of pulmonary hypertension and tachyarrythmia in hemodynamically significant defects, closure is necessary. Although surgery is considered a safe procedure with very low perioperative mortality, there is a risk of complications and prolonged hospitalization, and postoperative convalescence is two months. Today we are able to offer patients with ASD of the secundum type an alternative treatment using catheter technique. The devices used are self expanding and easy to deploy, with a high success rate and low complication rate. Post-procedural convalescence is two days.

Cardiac Catheterization↗

[Surgical mesh implantation in incisional hernia. A historical follow up study].

AIM OF STUDY: To describe risk factors, recurrence rates, morbidity and satisfaction in patients operated for incisional hernia with implantation of a surgical mesh. MATERIAL AND METHODS: The records of 60 patients undergoing an incisional hernia repair using a surgical mesh in the period 1.1.1993-30.6.1998 were reviewed, and 49 living patients were examined. RESULTS: During a mean follow-up of 27 months, patients with preoperative risk factors had more complications and recurrences. Overall recurrence rate was 14%. Ninety-six percent were satisfied with the operation and 90% wanted the same operation in case of recurrence. CONCLUSION: Operation for incisional hernia using implantation of a surgical mesh is a safe and well tolerated procedure, care must be taken in patients with risk factors.

Follow-Up Studies↗

Sexual conflict promotes speciation in insects.

Speciation rates among extant lineages of organisms vary extensively, but our understanding of the causes of this variation and, therefore, the processes of speciation is still remarkably incomplete. Both theoretical and empirical studies have indicated that sexual selection is important in speciation, but earlier discussions have focused almost exclusively on the potential role of female mate choice. Recent findings of postmating reproductive conflicts of interest between the sexes suggest a quite different route to speciation. Such conflicts may lead to perpetual antagonistic coevolution between males and females and may thus generate rapid evolutionary divergence of traits involved in reproduction. Here, we assess this hypothesis by contrasting pairs of related groups of insect species differing in the opportunity for postmating sexual conflict. Groups where females mate with many males exhibited speciation rates four times as high as in related groups where females mate only once. Our results not only highlight the general importance of postmating sexual selection in speciation, but also support the recent suggestion that sexual conflict is a key engine of speciation.

Animals↗

Comparison of two extraction methods independently developed on two conceptually different automated supercritical fluid extraction systems for the determination of polychlorinated biphenyls in sediments.

Two extraction methods that independently have been developed on conceptually different automated supercritical fluid extraction systems, ISCO SFX 3560 (syringe pump and liquid trapping) and Hewlett-Packard 7680T SFE (reciprocating pump and solid-phase trapping), were compared for the extraction of polychlorinated biphenyls from two Swedish sediments. The results demonstrated that the high-temperature ISCO method in some cases yields a more exhaustive extraction, but also less clean extracts due to co-extraction of unwanted matrix components which are all present in the trapping solvent. The medium-temperature Hewlett-Packard method may sometimes cause problems with quantitative recoveries, but on the other hand it yields very clean extracts due to the extra selectivity resulting from collection on a solid-phase trap.

Automation↗

Introducing selective supercritical fluid extraction as a new tool for determining sorption/desorption behavior and bioavailability of persistent organic pollutants in sediment.

This review article intends to introduce the possibility of utilizing selective supercritical fluid extraction (SFE) as a tool to study sorption/desorption processes and bioavailability of persistent organic pollutants (POP) in sediment. Sorption/desorption behavior and bioavailability studies of POPs is a large research area, but still many unsolved problems exists. Therefore novel approaches to investigate mechanistic behavior of POPs in sediments are needed. Present literature on SFE points to the fact that selective SFE measurements can improve our knowledge, and recent investigations have been performed that demonstrate this. Results obtained with selective SFE can be connected to desorption of POPs in sediments under natural conditions in aquatic ecosytems. The ultimate goal is to use selective SFE as a way to determine the bioavailable fraction present within a matrix. A few preliminary results are presented here which may serve as a starting point for future studies.

Adsorption↗

The evolution of polyandry: multiple mating and female fitness in insects.

Theory suggests that male fitness generally increases steadily with mating rate, while one or a few matings are sufficient for females to maximize their reproductive success. Contrary to these predictions, however, females of the majority of insects mate multiply. We performed a meta-analysis of 122 experimental studies addressing the direct effects of multiple mating on female fitness in insects. Our results clearly show that females gain directly from multiple matings in terms of increased lifetime offspring production. Despite a negative effect of remating on female longevity in species without nuptial feeding, the positive effects (increased egg production rate and fertility) more than outweigh this negative effect for moderate mating rates. The average direct net fitness gain of multiple mating was as high as 30-70%. Therefore, the evolutionary maintenance of polyandry in insects can be understood solely in terms of direct effects. However, our results also strongly support the existence of an intermediate optimal female mating rate, beyond which a further elevated mating rate is deleterious. The existence of such optima implies that sexual conflict over the mating rate should be very common in insects, and that sexually antagonistic coevolution plays a key role in the evolution of mating systems and of many reproductive traits. We discuss the origin and maintenance of nuptial feeing in the light of our findings, and suggest that elaborate and nutritional ejaculates may be the result of sexually antagonistic coevolution. Future research should aim at gaining a quantitative understanding of the evolution of female mating rates. Copyright 2000 The Association for the Study of Animal Behaviour.

Journal Article↗

Slow-motion theory of nuclear spin relaxation in paramagnetic low-symmetry complexes: A generalization to high electron spin

The slow-motion theory of nuclear spin relaxation in paramagnetic low-symmetry complexes is generalized to comprise arbitrary values of S. We describe the effects of rhombic symmetry in the static zero-field splitting (ZFS) and allow the principal axis system of the static ZFS tensor to deviate from the molecule-fixed frame of the nuclear-electron dipole-dipole tensor. We show nuclear magnetic relaxation dispersion (NMRD) profiles for different illustrative cases, ranging from within the Redfield limit into the slow-motion regime with respect to the electron spin dynamics. We focus on S = 3/2 and compare the effects of symmetry-breaking properties on the paramagnetic relaxation enhancement (PRE) in this case with that of S = 1, which we have treated in a previous paper. We also discuss cases of S = 2, 5/2, 3, and 7/2. One of the main objectives of this investigation, together with the previous papers, is to provide a set of standard calculations using the general slow-motion theory, against which simplified models may be tested. Copyright 2000 Academic Press.

Journal Article↗

Breaking the COPI monopoly on Golgi recycling.

The unexpected discovery of a transport pathway from the Golgi to the endoplasmic reticulum (ER) independent of COPI coat proteins sheds light on how Golgi resident enzymes and protein toxins gain access to the ER from as far as the trans Golgi network. This new pathway provides an explanation for how membrane is recycled to allow for an apparent concentration of anterograde cargo at distinct stages of the secretory pathway. As signal-mediated COPI-dependent recycling also involves the concentration of resident proteins into retrograde COPI vesicles, the main bulk of lipids must be recycled, possibly through a COPI-independent pathway.

Coat Protein Complex I↗

Relations between Helicobacter pylori, thyroid disease and cardiovascular risk factors in a 56-65-year-old population.

OBJECTIVE: To estimate the prevalence of and relation between Helicobacter pylori (HP) and thyroid disease in a 56-65-year-old population with cardiovascular risk factors. DESIGN: Cross-sectional study including every second individual in the age group. SETTING: The primary health care district of Mölnlycke, with about 14,000 inhabitants. PATIENTS: 170 men and 217 women aged between 56 and 65 years. MAIN OUTCOME MEASURES: Anthropometric (body mass index (BMI), waist/hip ratio (WHR)) and blood pressure measurements, biochemical analyses, including s-TSH, s-FT4 and HP serology. RESULTS: There was a high prevalence of metabolic risk factors in this pre-retirement group of individuals. The prevalence of HP was 42% in both men and women. Only a significant correlation between HP and WHR was seen in men. CONCLUSIONS: No reason could be found for including analysis of HP and thyroid tests in screening programmes for cardiovascular risk factors in men and women.

Age Distribution↗

Forearm blood flow responses to neuropeptide Y, noradrenaline and adenosine 5'-triphosphate in hypertensive and normotensive subjects.

Neuropeptide Y (NPY), noradrenaline (NA) and adenosine 5'-triphosphate (ATP) are important co-transmitters in the sympathetic nervous system, which has a central role in cardiovascular control. In order to evaluate if hypertension is associated with alterations in vascular responses to sympathetic co-transmitters we studied the effects of intra-arterial infusion of NPY, NA and ATP on forearm blood flow. Blood flow was measured by venous occlusion plethysmography in six hypertensive (mean arterial blood pressure (MAP) 113 +/- 4 mmHg) and six matched normotensive subjects (MAP 97 +/- 3 mmHg). NPY and NA significantly reduced forearm blood flow, while a powerful increase was seen with ATP. Forearm vascular resistance, calculated as MAP divided by forearm blood flow, was significantly increased by NPY and NA and strongly reduced by ATP. There was no difference between hypertensive and normotensive subjects in response to either transmitter. In conclusion, vascular reactivity to intra-arterial administration of NPY, NA and ATP seems to be intact in hypertensive patients without metabolic aberrations.

Adenosine Triphosphate↗

Vasodilation in human subcutaneous arteries induced by neuropeptide Y is mediated by neuropeptide Y Y1 receptors and is nitric oxide dependent.

Neuropeptide Y (NPY) is known as a potent vasoconstrictor of peripheral blood vessels both in vivo and in vitro. There have been reports suggesting that NPY also has a dilatory effect. The aim of the present study was to elucidate whether NPY dilates small human subcutaneous arteries. Subcutaneous arteries, obtained from patients undergoing abdominal surgery, were mounted in in vitro tissue baths, and the vascular responses to NPY were investigated. The presence of mRNA encoding the human NPY Y1 receptor in endothelial cells from human umbilical veins was studied by the use of reverse transcriptase - polymerase chain reaction (RT-PCR). In arteries precontracted with the prostaglandin analogue U46619, NPY induced a concentration-dependent vasodilation (Emax 30 +/- 10% of the U46619-induced contraction), which was significantly inhibited by the NPY Y1 receptor antagonist BIBP3226 (1 microM), causing a rightward shift of the concentration-response curve, pEC50 7.1 +/- 0.3 vs. 7.7 +/- 0.3 for NPY alone. After pretreatment with the nitric oxide synthetase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (10 microM), the dilation was abolished (Emax 6 +/- 5% of the U46619-induced contraction). mRNA encoding the human NPY Y1 receptor was detected in endothelial cells from human umbilical veins. It was concluded that NPY induces vasodilation in human subcutaneous arteries. The dilation is mediated via the NPY Y1 receptor and is dependent on nitric oxide.

Arginine↗

Neuropeptide Y stimulates DNA synthesis in human vascular smooth muscle cells through neuropeptide Y Y1 receptors.

We investigated the mitogenic effect, measured as [3H]thymidine incorporation, of neuropeptide Y (NPY) on smooth muscle cells (SMCs) from human subcutaneous arteries (diameter: 0.4 mm). NPY stimulated DNA synthesis in a concentration-dependent manner, Emax 32 +/- 5% relative to control. The effect was potently antagonised by the NPY Y1 receptor antagonist BIBP3226 ((R)-N2-(diphenylacetyl)-N-[(4-hydroxy-phenyl)methyl]-D-arginine-a mide), indicating the effect to be mediated via the NPY Y1 receptor. Noradrenaline (NA) also induced mitogenesis, Emax 35 +/- 10% relative to control. When added together, NPY and NA potentiated the [3H]thymidine incorporation, Emax 109 +/- 38% relative to control. Also, this effect seems to be mediated by the NPY Y1 receptor, since BIBP3226 blocked the effect (44 +/- 9% relative to control). The mitogenic effect of NPY and NA, two important transmitters of the sympathetic nervous system, might have clinical consequences on conditions with elevated sympathetic nerve activity.

Cells, Cultured↗

[Treatment of neonatal hyperbilirubinemia with BiliBed].

Phototherapy of the newborn is a common procedure in the neonatal ward. Different devices and lightsources are being used in the Scandinavian countries. In order to evaluate the safety and efficacy of a yet another new phototherapeutic device, the BiliBed, a randomised clinical, open cross-over study was undertaken. The study population comprised 22 newborn infants with non-haemolytic hyperbilirubinaemia. The effects of Bilibed on bilirubin elimination, fluid balance and restlessness during treatment were determined and compared to those obtained during conventional phototherapy. Heart rate and respiratory rate were used as a crude index of sympato-adrenerg tone during treatment. Both appliances were equally effective in reducing serum bilirubin concentration. Heart rate and respiratory rate were significantly lower during treatment with BiliBed. In spite of equal faecal/urinary output in conjunction with less ad libitum feeding volume, a trend towards better weight development was observed during BiliBed treatment. This may reflect differences in insensible water loss during treatment. The results suggest that BiliBed may be used without any disadvantages for the newborn compared to conventional phototherapy. Larger clinical trials are needed to determine its place in the clinical setting.

Body Weight↗

GTP hydrolysis by arf-1 mediates sorting and concentration of Golgi resident enzymes into functional COP I vesicles.

Upon addition of GTPgammaS to in vitro budding reactions, COP I vesicles form but retain their coat, making them easy to isolate and analyze. We have developed an in vitro budding assay that reconstitutes the formation of COP I-derived vesicles under conditions where GTP hydrolysis can occur. Once formed, vesicles are uncoated and appear functional as they fuse readily with acceptor membranes. Electron microscopy shows a homogeneous population of uncoated vesicles that contain the medial/trans Golgi enzyme alpha1, 2-mannosidase II. Biochemical quantitation of vesicles reveals that resident Golgi enzymes are up to 10-fold more concentrated than in donor membranes, but vesicles formed in the presence of GTPgammaS show an average density of resident Golgi enzymes similar to that seen in donor membranes. We show that the sorting process is mediated by the small GTPase arf-1 as addition of a dominant, hydrolysis-deficient arf-1 (Q)71(L) mutant produced results similar to that of GTPgammaS. Strikingly, the average density of the anterograde cargo protein, polymeric IgA receptor, in COP I-derived vesicles was similar to that found in starting membranes and was independent of GTP hydrolysis. We conclude that hydrolysis of GTP bound to arf-1 promotes selective segregation and concentration of Golgi resident enzymes into COP I vesicles.

ADP-Ribosylation Factor 1↗

The frequency of illegitimate TCRbeta/gamma gene recombination in human lymphocytes: influence of age, environmental exposure and cytostatic treatment, and correlation with frequencies of t(14;18) and hprt mutation.

Chromosome translocations in lymphoid malignancies often involve V(D)J recombinase mediated events giving rise to aberrant T-cell receptor (TCR) and immunoglobulin genes, which have been suggested to be useful as markers of genomic instability, genotoxic exposure and cancer risk. Illegitimate rearrangements involving the TCRbeta/gamma loci on chromosome 7 create TCRbeta/gamma hybrid genes which occur at low frequency in peripheral blood lymphocytes (PBLs) of normal healthy individuals. To evaluate the utility of this marker, we studied the possible effects of age and genotoxic exposures on the TCRbeta/gamma gene variant frequency (VF), and compared the frequencies of hypoxanthine guanine phosphoribosyl transferase (hprt) mutation, hprt exon 2/3 deletion, t(14;18) and TCRbeta/gamma gene rearrangements in cells from the same donors. The TCRbeta/gamma VF ranged five-fold among 16 middle aged blood donors with a mean of 0.74+/-0.29/10(5) PBLs, which is consistent with our previous estimate in healthy subjects. The TCRbeta/gamma VF was found to increase from birth until early adult life, and then to decrease with increasing age. Four testis cancer patients, who 6 years earlier had been treated with etoposide and other cytostatic drugs, showed TCRbeta/gamma VF similar to that in healthy controls. No increase of the TCRbeta/gamma VF was found among non-smoking PAH-exposed aluminum smelter workers compared to non-smoking controls. Smoking smelter workers showed decreased TCRbeta/gamma VF compared to non-smoking workers and controls, but in a follow-up study 2 years later the difference was no longer statistically significant, although the smoking smelter workers still showed a lower TCRbeta/gamma VF than the controls. No correlation was obtained between the TCRbeta/gamma VF and the t(14;18) or hprt mutant frequency (MF) in a group of healthy individuals. However, there was a statistically significant correlation between the TCRbeta/gamma VF and the hprt exon 2/3 deletion frequency in PBL DNA from the same donors. These results show that the TCRbeta/gamma VF in healthy individuals changes with age and correlates with the frequency of hprt exon 2/3 deletion, another marker of aberrant V(D)J recombination in T-cells. However, no effect of smoking or present or previous exposure to genotoxic agents on TCRbeta/gamma VF was observed in this study. Thus, further studies are needed to prove the utility of TCRbeta/gamma gene rearrangement as a marker of genotoxic exposure.

Adult↗

Characterisation of 5-HT receptors in human coronary arteries by molecular and pharmacological techniques.

5-Hydroxytryptamine (5-HT) can produce both vasoconstrictor and vasorelaxant effects in human coronary arteries and the response to 5-HT can be influenced by the presence of disease. The aim of the present study was to elucidate the 5-HT receptor subtypes responsible for mediating 5-HT-evoked contraction of human coronary arteries using pharmacological, molecular and immunocytochemical approaches. Normal human coronary arteries, with intact endothelium, were mounted in tissue baths, and the vascular responses to 5-HT and 5-HT receptor agonists were studied. The effects of 5-HT1 and 5-HT2 receptor antagonists on these responses were also studied. Expression of messenger ribonucleic acid (mRNA) encoding different 5-HT receptors in human coronary arteries, atrium, ventricle wall and epicardium was determined using reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. The expression of 5-HT1B or 5-HT1D receptor protein was studied using subtype selective antibodies and standard immunocytochemical techniques. The rank order of 5-HT receptor agonist potency in causing vasoconstriction was 5-carboxamido tryptamine, (5-CT) > zolmitriptan = BW183C91 (N10-desmethyl zolmitriptan) = alpha-methyl-5-hydroxytryptamine (alpha-CH3-5-HT) = 5-HT = sumatriptan > 2-methyl-5-hydroxytryptamine (2-CH3-5-HT) = 8-hydroxy-DPAT (8-OH-DPAT). Alpha-CH3-5-HT, 5-CT, 5-HT, zolmitriptan and BW 183C91 were significantly more potent (approximately 3-fold) than sumatriptan and 2-CH3-5-HT, which in turn were more potent than 8-OH-DPAT. Ketanserin and methiothepin (5-HT2 and 5-HT1 receptor antagonists, respectively) caused parallel rightward shifts of the concentration-effect curves to alpha-CH3-5-HT or 5-CT, respectively, without changing the maximum contractile response. In human coronary arteries, atrium. ventricle and epicardium. RT-PCR products corresponding to the human 5-HT2A, 5-HT1B and 5-HT1F receptors were expressed in high levels, mRNAs coding for 5-HT7, 5-HT1A and 5-HT1D receptors were only weakly expressed. No 5-HT1F receptor mRNA was detected. In coronary arteries there was a differential expression of 5-HT1B versus 5-HT1D receptor mRNAs, with 5-HT1B mRNAs being found in greater abundance. Dense 5-HT1B-immunoreactivity was detected on smooth muscle layer within coronary artery, however, 5-HT1D-immunoreactivity was not detected. It is concluded that 5-HT-evoked contraction of human coronary arteries is most probably mediated via the activation of both 5-HT1B and 5-HT2A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗