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G Nilsson

Publications and source records attributed to G Nilsson.

At least 91 records · Page 5Linked to original sources

Unique progastrin processing in equine G-cells suggests marginal tyrosyl sulfotransferase activity.

Previous studies have indicated that equine G-cell processing of progastrin differs from that of other species. Since the difference may be due to structural features, we have identified equine gastrin-17 and -34 (<ELGLQGSPHLVADLSKKQGPWLEKEEAAYGWMDF-NH2), and cloned a corresponding 451-bp cDNA that encodes a 107-amino-acid preprogastrin. Comparison with other mammalian gastrins shows a high degree of conservation, but instead of four or five acidic residues preceding the bioactive carboxyamidated C-terminal heptapeptide, equine gastrin contains the remarkable substitution of Lys for Glu in this presumed invariant region. In contrast with known mammalian gastrins, which are all significantly Tyr-sulphated, the equine antral gastrins are virtually non-sulphated. Transfection of the equine preprogastrin cDNA into an endocrine cell line resulted in highly sulphated gastrins, indicating that the absence of in situ sulphation is not due to the structure of gastrin, but occurs rather because the equine antral G-cells are unique with respect to tyrosyl sulfotransferase activity. Furthermore, the marginal sulphation may explain the high proportion of gastrin-34 versus gastrin-17 in the equine antrum, since tyrosyl sulphation has been shown to promote the endoproteolytic processing of prohormones.

Amino Acid Sequence↗

Synthetic peptide-containing surfactants--evaluation of transmembrane versus amphipathic helices and surfactant protein C poly-valyl to poly-leucyl substitution.

Pulmonary surfactant contains two hydrophobic proteins, SP-B and SP-C. With the aim of identifying synthetic SP-B and SP-C substitutes for replacement therapy of respiratory distress syndromes, we have studied two transmembrane peptides and two amphipathic peptides that are located in the plane of a phospholipid bilayer. One amphipathic peptide was designed by changing the amino acid sequence, but not the composition or size, of the 21-residue peptide KL4. This peptide, designated KL(2,3) from its spacing of nonpolar and polar residues, exhibited similar alpha-helical content as KL4 but was oriented along a phospholipid bilayer plane, in contrast to the transmembrane orientation of KL4 in the same environment. The second amphipathic peptide analyzed was succinyl-LLEKLLEWLK-amide (WMAP10). KL4 more efficiently accelerated the spreading of a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (Pam2GroPCho)/phosphatidylglycerol (PtdGro)/palmitic acid (PamOH), 68:22:9 (by mass), at an air/water interface than did any of the amphipathic peptides. Similarly, KL4, but not KL(2,3), when present in an interfacial monolayer composed of Pam2GroPCho/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol, 7:3 (by mass), increased lipid insertion from subphase vesicles. An SP-C analogue, SP-C(Leu), with all helical valyl residues in native SP-C replaced with Leu and the palmitoylcysteines at positions 5 and 6 replaced with Ser, but otherwise with essentially the same primary structure as the native peptide, was analyzed. SP-C(Leu) exhibited similar alpha-helical content as native SP-C and a transmembrane orientation and, in contrast to poly-valyl-containing synthetic peptides, it folds into a helical conformation after acid-induced denaturation. SP-C(Leu) accelerated the spreading of Pam2GroPCho/PtdGro/PamOH, 68:22:9 (by mass), almost identically to native SP-C, and lowered the surface tension during rapid cyclic film compressions in a pulsating bubble surfactometer to near zero and 43 mN/m at minimum and maximum bubble size, respectively. Airway instillation of 2% (by mass) SP-C(Leu) combined with Pam2GroPCho/PtdGro/PamOH in preterm rabbit fetuses improved dynamic lung compliance by about 30% compared with untreated controls.

Animals↗

Evaluation of enhanced high-resolution laser Doppler imaging in an in vitro tube model with the aim of assessing blood flow in separate microvessels.

An enhanced high-resolution laser Doppler imaging (EHR-LDI) technique intended for visualization of separate microvessels was evaluated by use of in vitro flow models. In EHR-LDI, a laser beam focused to a half-power diameter less than 40 microm successively scans the tissue under study in steps of 25 microm. Spatial blood flow variations within microvascular structures of 1.5 x 1.5 mm are rendered by 64 x 64 measurement sites. Individual microvessel diameters could be estimated and an average difference of 11 microm compared to microscopic measurements was obtained. For the flow algorithm used, the LDI output signal was found to scale linearly with average velocity (0-3.5 mm/s) when a plastic tube of inner diameter 175 microm was perfused with human blood (correlation coefficient 0.99). The LDI output signal was further found insensitive to hematocrit variations in the range 16-44%. Due to the limited laser light penetration in blood, a reduction in the LDI output signal was observed as the inner tube diameters were successively changed from 280 to 1400 microm.

Animals↗

Specific and sensitive detection of the EWS/FLI1 fusion protein in Ewing's sarcoma by Western blotting.

We applied Western blotting, using an antibody against the carboxy terminal of the FLI1 protein, for detection of the 68-kDa EWS/FLI1 fusion protein in cultured Ewing's sarcoma cells and in four surgical biopsies of Ewing's sarcoma. Of six different human cell lines, the 68-kDa fusion protein was identified only in Ewing's sarcoma cells carrying the t(11;22)(q24;q12) translocation. The four samples from Ewing's sarcoma patients were also found to contain the 68-kDa fusion protein. The lowest detection level for total protein loaded on the gel was 0.3 microg. When whole Ewing's sarcoma cells were used for Western blotting without prior protein extraction, the lowest detection level was 1,300 cells. It will be possible to use Western blotting for detection of the EWS/FLI1 fusion protein in the diagnosis of Ewing's sarcoma in surgical biopsy specimens, and possibly also in fine-needle aspirates. As the method is not dependent on the quality of mRNA in the sample and involves no risk of contamination, it will be a powerful complement to the reverse-transcription polymerase chain reaction (RT-PCR).

Blotting, Western↗

Demonstration of mast-cell chemotactic activity in nasal lavage fluid: characterization of one chemotaxin as c-kit ligand, stem cell factor.

Mast cells are known to accumulate in tissue during allergic inflammation. However, the chemotaxins responsible are undefined. Using a modified Boyden chamber and the human mast-cell line HMC-1, we first identified mast-cell chemotactic activity in nasal lavage fluid collected before the pollen season after allergen provocation of allergic patients (n=29) (mean migratory response compared to medium control was 121%, range 85-198%). Mast-cell chemotactic activity was also detected in lavage fluid collected after allergen provocation at the end of a Swedish birch-pollen season from three different treatment groups: topical steroid treatment with budesonide; the topical antihistamine, levocabastine; and placebo. There was no significant difference in mast-cell chemotactic activity between nasal lavage fluid collected from the placebo group (mean=102%), the budesonide-treated group (mean=114%), or the levocabastine group (mean=125%). Stem cell factor (SCF), a known mast-cell chemotaxin, was present in the nasal lavage fluids from all three groups, and correlated with the mast-cell chemotactic activity (r=0.67, P<0.01). The mast-cell chemotactic activity was inhibited (range 5-100%) in some, but not all, nasal lavage fluids by a polyclonal antibody directed against SCF. This report describes the presence of mast-cell chemotactic activity in nasal lavage fluid during an allergic reaction. These findings show that SCF may play a pivotal role in the recruitment of mast cells in allergic rhinitis.

Allergens↗

Semantic modeling of a traditional classification: results and implications.

A primary health care version of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), together with a three-dimensional model for classification of diseases according to location, origin, and type has been semantically represented. The resulting computer-based version is made available via the World Wide Web.

Disease↗

Effects of differently composed feeds and physical stress on plasma gastrin concentration in horses.

Plasma gastrin concentrations were determined in 6 Standardbreds (4 geldings and 2 mares) after 3 different meals consisting of unlimited amounts of hay (8-9 kg per horse), a restricted amount of hay (0.6 kg/100 kg body-weight) and grain (0.2 kg/100 kg body-weight) in combination or of grain alone (0.2 kg/100 kg body-weight). In another series of experiments the possible role of gastrin as a stress hormone was investigated. Plasma gastrin and cortisol concentrations were determined during fasting and compared with concentrations during hay feeding. In addition, gastrin and cortisol concentrations were determined before, during and after 2 kinds of physical exercise on a treadmill. Meal stimulation significantly increased the plasma gastrin concentration, irrespective of the meal composition. An immediate and large increase in plasma gastrin concentration was found when voluminous meals were given, whereas a small meal evoked a later onset of gastrin release, suggesting that gastric distention plays an important role in inducing gastrin release during a meal. Meals consisting of grain seem to evoke a slower onset and then a more prolonged gastrin response than a hay meal, possibly due to different emptying rates of the stomach. Nervous excitation may play a minor role in the activation of gastrin release in horses. No experimental support was obtained for the idea that gastrin acts as a stress hormone in the horse.

Animal Feed↗

The possibility of influencing components of hospital delay time within emergency departments among patients with ST-elevation in the initial electrocardiogram.

The aim of this study was to describe the possibility of influencing components of hospital delay time within the emergency department (ED) among patients with ST-elevation on the initial electrocardiogram (ECG). Nurses recorded seven patient time points: (1) ED admission; (2) ECG recording; (3) decision by nurse/ED physician; (4) cardiologist ED arrival; (5) decision of coronary care unit (CCU) admission; (6) ED departure; (7) CCU arrival. After special training in ECG, nurses in the ED were subsequently delegated to send patients directly to the CCU if showing ST-elevation on the admission ECG without contacting either the physician in ED or the cardiologist on call (intervention). Delay times between hospital admission and admission to the CCU were evaluated during the 9 months prior to and during the 6 months after the start of this intervention. Fifty patients (66% men) participated in the first study during 3 months (prior to intervention). Patients with suspected or confirmed acute myocardial infarction (AMI) in the ED had a median delay time from ED arrival to CCU arrival of 55.5 minutes (34.5 minutes for patients with confirmed AMI; ST elevation on admission). Time interval from decision to admit to CCU and ED departure was an average of 31% of the total delay. A mean of 21% of total delay occurred between ED decision to cardiologist arrival, and 19% during the time interval from cardiologist ED arrival until decision to CCU admission. Among patients receiving thrombolysis, the median delay time from hospital admission to CCU admission was reduced from 40 minutes during the 9 months prior to start of the intervention (nurses sending patients directly to the CCU) to 22 minutes during the 6 months thereafter (p = 0.02). The largest proportion of hospital delay components for acute coronary syndrome patients occurred between the cardiologist's decision to admit to the CCU and departure from the ED, and the interval following the decision by the nurse or physician to the cardiologist ED arrival. When nurses were delegated to transfer patients with ST-elevation on admission directly to the CCU without contacting a physician, the delay time from ED admission to CCU admission was reduced by nearly 50%.

Adult↗

Human mast cells express functional TrkA and are a source of nerve growth factor.

Mast cells are the principal effector cells in IgE-dependent hypersensitivity reactions. Despite reports that rodent mast cells proliferate in the presence of nerve growth factor (NGF), human mast cells reportedly do not respond to this factor. To determine if human mast cells express the NGF receptors, TrkA tyrosine receptor and the low affinity NGF receptor (LNGFR), we first analyzed the mRNA expression by RT-PCR of TrkA and LNGFR in a human mast cell line (HMC-1) and in human mast cells cultured in the presence of stem cell factor. Both HMC-1 and cultured human mast cells were found to express TrkA but not LNGFR. TrkA protein was demonstrated by Western blot analysis of HMC-1 lysates. Using flow cytometric analysis and mast cell tryptase as a mast cell marker, both HMC-1 cells and cultured human mast cells were shown to coexpress tryptase and TrkA. Treatment of mast cells with NGF resulted in phosphorylation of TrkA on tyrosine residues as detected by immunoblotting with an antiphosphotyrosine antibody. Furthermore, NGF induced the immediate early gene c-fos in HMC-1 cells. HMC-1 cells and cultured human mast cells were also found to express NGF mRNA, and conditioned medium from HMC-1 cells stimulated neurite outgrowth from chicken embryonic sensory ganglia in culture. This effect was blocked by anti-NGF. Thus, mast cells express functional TrkA and synthesize NGF, suggesting a mechanism by which NGF may act as an autocrine factor for human mast cells, and by which mast cells and nerves may interact.

Cell Communication↗

Cold caloric microcirculatory reflex disturbance in patients with Parkinson's disease.

The basal skin microcirculatory blood flow and its change in response to a cold caloric stimulus (cold water, 5 degrees C, exposure of one foot for 30 s) were investigated in nine patients with Parkinson's disease (PD) and nine normal subjects (controls). The results revealed a significant (p < 0.001) difference between the groups. In the controls there was a strong decrease in the red cell flux (RCF) on cold water exposure, while eight of the nine PD patients revealed no detectable change in RCF; in one patient only there was a less pronounced reaction. It was concluded that the regulation of the microcirculatory blood flow was affected in PD patients; the cold caloric reflex was attenuated or absent but there was no difference in the basal microcirculatory blood flow compared to normal subjects.

Aged↗

New approach for elucidating the oxygen sensitivity and calibration of the antimony electrode.

The biomedical use of the polycrystalline antimony pH electrode is hampered by oxygen dependence and low pH resolution (0.1 pH). Although, the pH resolution is improved by using highly purified crystallographically oriented monocrystalline antimony (COMA), the oxygen effect on the electrode remains. In an in vitro examination of the COMA electrode it was found that the oxygen dependence is similar to that of polycrystalline antimony, i.e. nonlinear with an increase in sensitivity below 10 kPa. These findings imply that the oxygen tension in the vicinity of a COMA pH electrode, has to be known or controllable for the pH reading to be at all valid especially at low oxygen levels, such as is often seen in biomedical applications. A calibration procedure using a zero oxygen solution is used in order to obtain absolute pH readings in a measurement solution of pre-set or known oxygen levels. Furthermore, the nonlinear oxygen sensitivity of the antimony electrode suggests that the underlying electrochemical reactions are other than those described by corrosion theory.

Antimony↗

Responses in skin microcirculation to vestibular stimulation before and during motion sickness.

BACKGROUND: Observation of physiological changes during motion sickness is required to quantify the degree of sickness. The review of the literature does not show unifying results. An objective symptom of motion sickness is facial pallor. It reflects changes in skin microcirculation which have not been measured so far. METHODS: Eleven healthy volunteers susceptible to motion sickness were subjected to eccentric vertical axis rotation. The dynamics and the correspondence of the changes in skin blood flow in two segments, forehead and finger, were measured by laser Doppler flowmeter. RESULTS AND CONCLUSIONS: The difference in the microcirculatory skin blood flow across the phases of motion sickness is significant for the forehead but not for the fingertip: the established dynamics of the forehead blood flow during motion sickness will be of benefit in quantifying the degree of sickness; there is no correlation between the blood flow changes in both measured areas; the rhythmic blood flow fluctuation increases during motion sickness; there is a difference between the blood flow responses to vestibular stimulation before the appearance of motion sickness and in the course of the sickness. Laser Doppler flowmetry is a reliable method in quantifying the degree of motion sickness.

Adult↗

Interleukin-15 + thioredoxin induce DNA synthesis in B-chronic lymphocytic leukemia cells but not in normal B cells.

We have previously shown that Staphylococcus aureus Cowan strain 1 particles (SAC) + thioredoxin (Trx) + IL-2 may induce B-chronic lymphocytic leukemia (B-CLL) cells to proliferate. In this paper we have examined IL-15, which has activities similar to IL-2, for its ability to stimulate B-CLL cells and compared its activity with that of IL-2. We found that B-CLL cells could be induced to DNA synthesis upon treatment with IL-15 + Trx. The presence of Trx was essential for the IL-15-induced DNA synthesis. This contrasts to the effect of IL-15 + Trx on normal CD5+ and CD5- B cells, where IL-15 + Trx alone only induced limited DNA synthesis. IL-15 was as effective in the induction of DNA synthesis in B-CLL cells as IL-2, but about 100-fold less potent with an EC50 of 200 ng/ml. In addition we found that the IL-15 + Trx-induced proliferation was inhibited by CD40 stimulation. We conclude that IL-15 together with a proper costimulus can induce B-CLL cells to proliferate in vitro.

B-Lymphocytes↗

Cerebral blood flow of the exposed brain surface measured by laser Doppler perfusion imaging.

A novel application of laser Doppler flowmetry (LDF) laser Doppler perfusion imaging (LDPI), was used to study cerebral cortical blood flow (CBFcortex). In contrast to the conventional laser Doppler perfusion monitor, LDPI creates two dimensional maps of the tissue perfusion in a well defined area of up to 120 x 120 mm comprising 4096 measurements points. Measurements of CBFcortex were made through an optically transparent polyester film applied to a cranial window preparation in ventilated anaesthetized pigs. Temporal and spatial heterogeneity in CBFcortex were visualized by LDPI during provocations which are known to alter CBF (varying arterial PCO2 or MABP, or infusion of adenosine at constant MABP (concomitant angiotensin administration) or by hyperoxemia). During hypercapnia the recorded CBFcortex increased homogeneously. The adenosine-mediated increase in recorded CBFcortex was concentrated on the lower flow interval, as was the hyperoxemia-caused decline. At decreasing MABP the autoregulatory threshold was found to vary locally within the cortex. The results suggest that LDPI, apart from detecting localized changes in CBFcortex' also visualizes flow changes within different vascular segments. Together with the practical advantages of the system, i.e. not necessitating direct contact with the tissues, this feature makes the technique suitable for studies of CBFcortex distributions.

Animals↗

Heterogeneous blood flow response in the foot on dependency, assessed by laser Doppler perfusion imaging.

The exact nature of the decrease in foot skin blood flow seen after a change in posture remains unsettled. This mechanism has previously been examined by non-invasive techniques such as the laser Doppler perfusion monitor (laser Doppler flowmetry). Taking into account the shortcomings of laser Doppler perfusion monitoring when applied to the determination of skin blood flow, which normally shows substantial heterogeneity, we have applied an emerging technology, the laser Doppler perfusion imager (LDPI). This technique provides a more comprehensive picture of the blood flow distribution in the skin, as it maps skin blood flow over a surface area (120 x 120 mm, 4096 measurement sites). It was used to examine if the reduction in tissue perfusion or the alterations in flow distributions seen after a change in posture (supine to dependency) could be fully explained by an increase in venous pressure (venous stasis of 50 mmHg) or if the data suggest a complementary mechanism. Skin blood flow of the forefoot decreased from 0.60 V (volt) (median) during rest to 0.40 and 0.38 V during venous stasis and dependency, respectively. Although almost identical median values were obtained during stasis and dependency, the flow distributions were different with a loss of high flow values during venous stasis. Biological zero was 0.24 V. As the LDPI technique readily records skin perfusion during variations in venous stasis and posture, as well as information on flow distribution changes. It appears promising for future application in stimuli-response studies of skin blood flow. The difference in flow distribution seen between increased venous pressure and dependency suggests an additive regulatory mechanism to the veni-vasomotor reflex during a change in posture.

Adult↗