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Biomedical subjects

M Gustafsson

Publications and source records attributed to M Gustafsson.

At least 37 records · Page 2Linked to original sources

A qualitative study of stress factors in the early stage of acute traumatic hand injury.

The aim of the study reported in this paper was to identify stress factors in the early stage of acute traumatic hand injury. Stress factors were defined as circumstances which the hand-injured patients experienced as problems in the actual situation. A total of 20 patients, treated as inpatients at the Department of Hand Surgery in Orebro Medical Centre Hospital, Sweden, were interviewed 8-20 days after the day of the accident. The analyses of the interviews followed the first step in the analytical process described in a modified model of grounded theory. The trauma experience was one of the stress factors in the early stage. Single acute traumatic stress symptoms, mostly involuntary recollection and re-experience of the trauma, were found in a fourth of the hand-injured patients. All patients reported impaired functioning caused by their hand, irrespective of injury. Practical problems with daily activities and being dependent on help from others for solving practical problems were stress factors caused by functional impairment. Before the accident most of the hand-injured had been very active, also working a lot with their hands in their leisure-time. Involuntary inactivity was a big problem for some of them. Other stress factors in the early stage were uncertainty about function in the future and pain. The appearance of the hand was a minor problem before the first follow-up visit. Probably because the hand was hidden in a bandage. However, some hand-injured felt discomfort in seeing the hand when the dressing was changed at the first follow-up visit.

Activities of Daily Living↗

A role for the fibrinogen-binding regions of streptococcal M proteins in phagocytosis resistance.

All virulent group A streptococcal isolates bind fibrinogen, a property that is closely linked to expression of type-specific antiphagocytic surface molecules designated M proteins. Here we show that although the M proteins from two different strains, M1 and M5, both bind fibrinogen with high affinity, they interact with different regions in the ligand. Moreover, mapping experiments demonstrated that the fibrinogen-binding regions in the M1 and M5 proteins are quite dissimilar at the amino acid sequence level and that they bind to different regions in the plasma protein. In spite of these differences, the fibrinogen-binding regions of M1 and M5 could both be shown to contribute to streptococcal survival in human blood, providing evidence for the distinct function of a plasma protein interaction in bacterial pathogenesis.

Amino Acid Sequence↗

Dynamic ca(2+)changes in neutrophil phagosomes A source for intracellular ca(2+)during phagolysosome formation?

An increase in cytosolic Ca(2+)concentration periphagosomally is critical for phagolysosomal formation and neutrophil elimination of microbes. The Ca(2+)increase could be achieved through release of Ca(2+)from mobilized intracellular stores. Alternatively, Ca(2+)that passively enter the phagosome during phagocytosis could be provided by the phagosome. Intraphagosomal Ca(2+)changes in single human neutrophils was measured during phagocytosis of serum opsonized Fura-2-conjugated zymosan particles, using a digital image processing system for microspectrofluorometry. A decrease in phagosomal Ca(2+)down to nanomolar concentrations was seen within minutes following phagosomal closure. Blockage of plasma membrane Ca(2+)channels by econazole abolished this decrease. The fluorescence properties of Fura-2 zymosan were retained after phagocytosis and stable to pH changes, reactive oxygen species, and proteolytic enzymes. We suggest that Ca(2+)ions present in the phagosome enter the cell cytosol through Ca(2+)channels in the phagosomal membrane, achieving a localized Ca(2+)rise that is important for phagosome processing.

Calcium↗

Role of extracellular retention of low density lipoproteins in atherosclerosis.

The pathogenesis for atherosclerosis is still unclear, and several hypotheses have been articulated to explain the initiating events in atherogenesis. Although these hypotheses are by no means mutually exclusive, there is a growing body of recent evidence that has led to the concept that subendothelial retention of apolipoprotein B100-containing lipoproteins is the initiating event in atherogenesis. Subsequently, a series of biological responses to this retained material leads to specific molecular and cellular processes that promote lesion formation. The present review assesses some of the studies that support this concept.

Animals↗

An optimization approach to multi-dimensional time domain acoustic inverse problems.

An optimization approach to a multi-dimensional acoustic inverse problem in the time domain is considered. The density and/or the sound speed are reconstructed by minimizing an objective functional. By introducing dual functions and using the Gauss divergence theorem, the gradient of the objective functional is found as an explicit expression. The parameters are then reconstructed by an iterative algorithm (the conjugate gradient method). The reconstruction algorithm is tested with noisy data, and these tests indicate that the algorithm is stable and robust. The computation time for the reconstruction is greatly improved when the analytic gradient is used.

Acoustics↗

Amyloid fibril formation by pulmonary surfactant protein C.

Lung surfactant protein C (SP-C) is a lipopeptide that contains two fatty acyl (palmitoyl) chains bound via intrinsically labile thioester bonds. SP-C can transform from a monomeric alpha-helix into beta-sheet aggregates, reminiscent of structural changes that are supposed to occur in amyloid fibril formation. SP-C is here shown to form amyloid upon incubation in solution. Furthermore, one patient with pulmonary alveolar proteinosis (PAP, a rare disease where lung surfactant proteins and lipids accumulate in the airspaces) and six healthy controls have been studied regarding presence and composition of amyloid fibrils in the cell-free fraction of bronchoalveolar lavage (BAL) fluid. Abundant amyloid fibrils were found in BAL fluid from the patient with PAP and, in low amounts, in three of the six healthy controls. SDS-insoluble fibrillar material associated with PAP mainly consists of SP-C, in contrast to the fibrils found in controls. Fibrillated SP-C has to a significant extent lost the palmitoyl groups, and removal of the palmitoyl groups in vitro increases the rate of fibril formation.

Adolescent↗

Pain, coping and analgesic medication usage in rheumatoid arthritis patients.

The major purposes of this study were to describe pain characteristics and coping strategies used in rheumatoid arthritis (RA) patients. Further purposes were to examine relationships among pain, coping and analgesic medication intake. Sixty-eight consecutively sampled subjects with RA participated in the study. The Pain-O-Meter was used to evaluate pain intensity and quality, and the Coping Strategies Questionnaire (CSQ) to determine coping strategies. The results showed that the patients with RA scored more intense sensory than affective pain although they used more affective pain descriptors. The sensory and total pain components were related to coping self-statements and increased pain activities. There were significant relationships between analgesic medication intake and all coping strategies used in the RA patients. The findings' implication for education and treatment are discussed.

Adaptation, Psychological↗

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↗

Analysis of variant forms of porcine surfactant polypeptide-C by nano-electrospray mass spectrometry.

Electrospray (ES) mass spectrometry has been used to analyse preparations of porcine pulmonary surfactant polypeptide-C (SP-C). A number of variant forms of the native 35-residue dipalmitoylated peptide were detected including (a) C-terminally methylated SP-C, (b) C-terminally methylated and methionine oxidized SP-C, (c) N-terminally truncated, C-terminally methylated and methionine oxidized SP-c, (d) C-terminally elongated, C-terminally methylated and methionine oxidized SP-C, and (e) tripalmitoylated, C-terminally methylated and methionine oxidized SP-C. C-terminal methylation and methionine oxidation are probably a consequence of the sample handling procedure. The occurrence of the C-terminally elongated form of SP-C has implications for the in vivo processing of proSP-C and the Tandem mass spectrometry (MS/MS) was used to confirm the amino acid sequence of SP-C and the presence of palmitoyl groups covalently linked to the peptide. Some of the structures of the variant forms of SP-C were determined by MS/MS.

Amino Acid Sequence↗

Teat massage after milk ingestion in domestic piglets: an example of honest begging?

After milk ejection, piglets spend several minutes massaging their own teats on the sow. We examined whether this behaviour could be a mammalian counterpart to begging in young birds, and hence be explained by theories of honest begging. In one experiment, the behaviour of piglets was examined in relation to their previous milk intake. In each of 16 litters, one focal piglet was exposed to three treatments for three consecutive sucklings: 'no milk', where the piglet was withheld from the teat during milk ejection; 'extra milk', where it was fed 10 ml of extra milk directly after milk ejection; and 'control', when it received its normal intake. Average massage duration in the next three sucklings was significantly longer in the 'no milk' than in the control piglets. 'No milk' pigs massaged more intensely (number of massage movements/min), were more persistent in attempting to maintain udder contact and spent less time away from the udder. However, there were no significant differences between 'control' and 'extra milk' treatments. In a second experiment, in which we manually massaged teats for 0, 3 or 10 min, we found no significant effect of massage duration on milk output (measured by weighing piglets before and after milk ejection), although massage tended to increase output. We conclude that post-sucking massage in piglets has a number of aspects similar to honest begging in birds. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

Synthetic surfactant protein analogues.

Surfactant preparations for the treatment of respiratory distress syndrome (RDS) that contain phospholipids and small amounts of the two hydrophobic proteins, SP-B and SP-C, are presently obtained from animal lungs. Since structural information about SP-B and SP-C is available, it appears possible to design analogues that can replace the native proteins in synthetic surfactants. SP-C contains a single helix, but analogues with the poly-Val sequence of the native molecule do not fold into a native-like alpha-helical conformation. However, replacement of all Val with Leu yields efficient folding into a helical structure and Leu-based SP-C analogues effectively accelerate spreading of surfactant lipids and exhibit some physiological activity in animal models of RDS. The inferior in vivo activity of synthetic surfactants containing SP-C only compared to that of surfactant preparations derived from natural sources may be caused by a lack of covalently linked palmitoyl groups in the analogues and/or absence of SP-B. SP-B is significantly larger than SP-C and has a tertiary fold of several amphipathic helices in a dimeric structure. A single simplified amphipathic helical peptide containing only Leu and Lys does not mimic the surface properties of SP-B in vitro. These circumstances make the design of SP-B analogues from solely structural considerations less likely to be successful than in the case of SP-C.

Drug Design↗

Efficiency of cytological screening for detection of cervical squamous carcinoma. A study in the county of Uppsala 1991-1994.

Squamous carcinoma of the uterine cervix accounts for a considerable mortality among gynecological malignancies, although both the incidence of and mortality from cervical cancer have decreased in the Nordic countries since 1970. The reduction is a result of the cytologic screening program, through which precursor lesions can be detected and removed. Our aim was to determine why women in the county of Uppsala get cervical cancer despite extensive gynecological screening. A retrospective study of all women (43 cases) who developed histologically verified cervical squamous carcinoma in the county of Uppsala during the years 1991 to 1994 was undertaken. A central computer database covering all histopathological and cytological material made it possible to compare each woman's previous smears or lack of smears with her cancer diagnosis. Twenty women (47%, mean age at diagnosis 64.4 years) had not undergone cytological screening. Twenty-three women (53%) had been screened at least once within 6 years before tumor diagnosis. Of these, 11 (mean age 47.5 years) had had normal smears for the last 6 years, 8 (mean age 44.3 years) had shown abnormal cytology for less than one year and 4 (mean age 39.0 years) had shown abnormal cytology for more than one year and up to 6 years before their cervical cancer diagnosis. Women with cervical squamous carcinoma, who are not covered by the gynecological screening program (47%) are at increased risk of developing cervical cancer compared with other women. Consequently the average age of non-screened women developing cancer is considerably higher (64.4 years) than that of women with cancer screened previously (44.9 years). In 26% of the total group of women with cervical squamous carcinoma previous cytology displayed normal features.

Adult↗

Reverse-phase HPLC of the hydrophobic pulmonary surfactant proteins: detection of a surfactant protein C isoform containing Nepsilon-palmitoyl-lysine.

A reverse-phase HPLC protocol for analysis of strictly hydrophobic peptides and proteins was developed. Peptide aggregation is minimized by using only 25-40% water in methanol or ethanol as initial solvents and subsequent elution with a gradient of propan-2-ol. Analysis of the pulmonary surfactant-associated proteins B (SP-B) and C (SP-C) with this method reveals several features. (1) SP-B and SP-C retain their secondary structures and separate by about 15 min over a 40 min gradient. SP-B is more hydrophilic than SP-C, which in turn behaves chromatographically like palmitoyl-ethyl ester. (2) SP-C exhibits isoforms additional to the major form characterized previously, which contains two thioester-linked palmitoyl groups. The isoforms now observed contain one or three palmitoyl moieties and constitute together 15-20% of the major form. The tripalmitoylated species contains a palmitoyl group linked to the epsilon-amino group of Lys-11, as concluded from the elution position,MS and amino acid sequence analysis. The tripalmitoylated form increases relative to the dipalmitoylated form on incubation of SP-C ina phospholipid environment. An Nepsilon-bound palmitoyl moiety constitutes a third mode of fatty acyl modification of proteins, in addition to the established Nalpha-bound myristoyl groups and S-bound palmitoyl chains. (3) The dimeric structure of SP-B, lacking covalent modifications, is confirmed by MS detection of the dimer. No SP-B isoforms were detected. (4) Denatured, non-helical SP-C can be distinguished chromatographically from the native alpha-helical peptide. (5) HPLC of SP-C at 60-75 degrees C reveals an isoform containing an extra 14 Da moiety compared with the main form. This is concluded to arise from inadvertent methyl esterification of the C-terminal carboxy group. In conclusion, this HPLC method affords a sensitive means of assessing modifications and conformations of SP-B or SP-C in different disease states and before functional studies. It might also prove useful for analysis of other strictly hydrophobic polypeptides.

Animals↗

Incidence of long-term sick-listing in an urban area of Sweden and its relationship with demographic data of the population.

By checking the card indexes of seven out of twelve Social Insurance Offices covering 66% of the total wage-earning population in the city of Göteborg the patients recorded for 90 days of continuous sick-listing were classified into four diagnostic categories according to the doctor's certificate: "non-specific pain" and "specific pain" of the musculoskeletal system, "other pain" and "non-pain" diagnoses. The overall yearly incidence of 90 days' sick-listing averaged 5.4%. A significant correlation was found between the incidence of 90 days' sick-listing due to "non-pain" and musculoskeletal pain diagnoses and the proportion of demographic characteristics of the areas. The hypothesis of presuming the highest association between non-specific pain diagnoses and demographic factors was rejected.

Child↗

Long-term follow up after sex reassignment surgery.

A long-term follow up of 136 patients operated on for sex reassignment was done to evaluate the surgical outcome. Social and psychological adjustments were also investigated by a questionnaire in 90 of these 136 patients. Optimal results of the operation are essential for a successful outcome. Personal and social instability before operation, unsuitable body build, and age over 30 years at operation correlated with unsatisfactory results. Adequate family and social support is important for postoperative functioning. Sex reassignment had no influence on the person's ability to work.

Adult↗

Modulation of virulence factor expression by pathogen target cell contact.

Upon contact with the eukaryotic cell, Yersinia pseudotuberculosis increased the rate of transcription of virulence genes (yop), as determined by in situ monitoring of light emission from individual bacteria expressing luciferase under the control of the yopE promoter. The microbe-host interaction triggered export of LcrQ, a negative regulator of Yop expression, via the Yop-type III secretion system. The intracellular concentration of LcrQ was thereby lowered, resulting in increased expression of Yops. These results suggest a key role for the type III secretion system of pathogenic bacteria to coordinate secretion with expression of virulence factors after physical contact with the target cell.

Bacterial Adhesion↗