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J Johansson

Publications and source records attributed to J Johansson.

At least 127 records · Page 7Linked to original sources
PubMed1997

Laser-induced fluorescence studies of the biodistribution of carotenoporphyrins in mice.

The biodistribution of two recently developed tumour markers, trimethylated (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour-bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after administration, the carotenoporphyrin fluorescence was measured in tumoral and peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities. The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the first one is close to the peak of the tissue autofluorescence. The tumour and the liver were the two tissue types showing the strongest carotenoporphyrin-related fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak substance-related fluorescence. In most tissue types, the fluorescence intensities decreased over time. A few exceptions were observed, notably the liver, in which the intensity remained remarkably constant over the time period investigated.

Animals↗
PubMed1997

Correction factors for parallel-plate chambers used in plastic phantoms in electron dosimetry.

In electron beam dosimetry using parallel-plate chambers solid phantoms are sometimes necessary. To obtain the dose to water from the ionization obtained in the solid phantom, fluence correction factors and perturbation factors have to be applied. In this study fluence factors in a perturbation free geometry have been determined experimentally for common phantom materials. Wall perturbation factors for simulated Attix, NACP, and Roos chambers have also been determined for the same materials. Comparative Monte Carlo calculations have been performed using the EGS4 Monte Carlo code. Comparison with data in newly published protocols such as IAEA and IPEMB shows an agreement with the results obtained in this paper to within 1%, demonstrating that the data published in these protocols may be used with reasonable accuracy if recommended phantoms are used. The results also show that if unsuitable phantom materials are used, the wall perturbation factors may differ for different chambers and for different phantom materials by more than 3% and perturbation factors have to be considered in order to obtain a high accuracy in the dose determination.

Dose-Response Relationship, Radiation↗
PubMed1997

Vascular function correlates with risk factors for cardiovascular disease in a healthy population of 35-year-old subjects.

OBJECTIVE: To investigate whether, in a healthy, randomly selected population of 35-year-old men and women, there is a relation between vascular function and conventional risk factors for cardiovascular disease such as gender, smoking, elevated blood-lipids, high blood pressure and heredity for cardiovascular disease, and to blood glucose. DESIGN: Basal brachial artery diameter was measured. Endothelial function was measured as flow mediated dilation (FMD) in response to reactive hyperaemia. The nonendothelial dependent dilation was measured after sublingual nitro-glycerine (NTG). SETTING: A research centre of general medicine and a university hospital. SUBJECTS: One hundred men and 100 women all 35 years old, were invited by letter. Sixty-six of the 92 men (72%) living in the community and 74 of the 88 women (84%) participated. RESULTS: Gender had the largest influence on FMD and NTG induced arterial dilation, probably reflecting the larger vessel diameters in the men as FMD and NTG induced dilation is inversely related to basal vessel size (r = -0.55, P < 0.001 and r = -0.40, P < 0.001). In women basal vessel diameter was positively correlated to blood glucose (r = 0.35, P = 0.009) and BMI (r = 0.34, P = 0.012) and negatively correlated to HDL cholesterol (r = -0.43, P = 0.001). FMD and NTG induced arterial dilation correlated with a combined risk factor score (r = -0.32, P = 0.019 and r = -0.31, P = 0.024). The men with the highest risk factor scores had larger vessel size and higher blood flow at rest compared to men without risk factors (4.8 +/- 0.6 mm, 240 +/- 84 mL min-1 and 4.0 +/- 0.8 mm, 139 +/- 72 mL min-1, respectively, P = 0.014 and P = 0.016). FMD or NTG induced dilation did not correlate to any of the risk factors in men. CONCLUSIONS: There are correlations between vascular reactivity and risk factors for IHD in women and correlations between vessel diameter and risk factors for IHD in both men and women already in a healthy population 35-year-old subjects. Further studies are needed to determine if the vessel diameter in itself, in a healthy population, is a sign of attenuated endothelial function.

Adult↗
PubMed1996

The effect of probucol on low density lipoprotein oxidation and femoral atherosclerosis.

The Probucol Quantitative Regression Swedish Trial (PQRST) investigated the effect of the lipid lowering and antioxidant drug probucol on the development of atherosclerosis in humans. 303 hypercholesterolemic patients were randomized to receive either probucol or placebo, in combination with dietary advice and cholestyramine for a three-year period. Probucol was not found to effect progression regression of femoral atherosclerosis significantly as assessed by quantitative arteriography. To evaluate the effectiveness of probucol as an antioxidant during the study period, detailed analyses were performed on 42 of the randomized patients. During the trial, probucol-treated patients (n = 26) had 15% lower total cholesterol (P < 0.01) and 35% lower high density lipoprotein (HDL) cholesterol (P < 0.0001) compared with controls (n = 16). Low density lipoprotein (LDL) from probucol treated individuals was more resistant to oxidation by Cu2+ as determined by the lag phase for the formation of conjugated dienes (220 +/- 8 vs. 82 +/- 7 min (mean +/- S.E)), showed a 13 times lower formation of lipid peroxides, a 97% reduction in macrophage degradation and close to 90% less decrease in LDL receptor binding following oxidation as compared with controls (P < 0.001 for all differences). The results demonstrate that although probucol provided a significant protection against Cu(2+)-induced oxidative modification of LDL, it lacked effect on the development of femoral atherosclerosis. The relevance of these observations for the proposed role of lipid oxidation in atherosclerosis is discussed.

Adult↗
PubMed1996

The 21-residue surfactant peptide (LysLeu4)4Lys(KL4) is a transmembrane alpha-helix with a mixed nonpolar/polar surface.

The 21-residue peptide KLLLLKLLLLKLLLLKLLLLK (KL4) has been synthesized and analyzed regarding its secondary structure and orientation in lipid environments. Fourier transform infrared and circular dichroism spectroscopy shows that the peptide exhibits approximately 80% alpha-helical content both in dodecylphosphocholine micelles and in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/phosphatidylglycerol (PG) 7:3 (w/w) bilayers. The positively charged lysine residues are evenly distributed over the entire, otherwise nonpolar, circumference of the helix. This is in sharp contrast to the uneven distribution of polar and nonpolar residues in amphipathic helices. Fourier transform infrared spectroscopy of the peptide inserted in DPPC/PG bilayers shows that the helical axis is oriented parallel to the lipid acyl chains. These data do not support a previous hypothesis that the KL4 peptide interacts with peripheral parts of a phospholipid monolayer and mimics the pulmonary surfactant protein SP-B, which is composed of several amphipathic alpha-helices. KL4 accelerates the spreading of phospholipid mixtures at an air/water interface but does so less efficiently than other transmembranous helical polypeptides studied.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1996

Arrest of beta-amyloid fibril formation by a pentapeptide ligand.

Polymerization of amyloid beta-peptide (Abeta) into amyloid fibrils is a critical step in the pathogenesis of Alzheimer's disease. Here, we show that peptides incorporating a short Abeta fragment (KLVFF; Abeta16-20) can bind full-length Abeta and prevent its assembly into amyloid fibrils. Through alanine substitution, it was demonstrated that amino acids Lys16, Leu17, and Phe20 are critical for binding to Abeta and inhibition of Abeta fibril formation. A mutant Abeta molecule, in which these residues had been substituted, had a markedly reduced capability of forming amyloid fibrils. The present data suggest that residues Abeta16-20 serve as a binding sequence duringA beta polymerization and fibril formation. Moreover, the present KLVFF peptide may serve as a lead compound for the development of peptide and non-peptide agents aimed at inhibiting Abeta amyloidogenesis in vivo.

Amino Acid Sequence↗
PubMed1996

Adenocarcinoma in the distal esophagus with and without Barrett esophagus. Differences in symptoms and survival rates.

OBJECTIVE: To evaluate differences in clinical appearance and survival rates in patients operated on for adenocarcinoma in the distal esophagus with and without Barrett epithelium. DESIGN: Prospective clinical study. SETTING: University hospital, Sweden. PATIENTS: Fifty-four patients with adenocarcinoma in the distal esophagus with (n = 17) or without (n = 37) Barrett epithelium. INTERVENTION: Esophagectomy or total gastrectomy. MAIN OUTCOME MEASURES: Preoperative symptoms, endoscopic results, and histological findings; postoperative morbidity, mortality, and survival rates. RESULTS: The main indication for the endoscopic examination that revealed tumor in the group with Barrett esophagus was reflex-related symptoms in 6 patients (routine Barrett examination, n = 4; symptoms of reflux, n = 2), symptoms related to upper gastrointestinal tract bleeding in 6, and malignant symptoms in 5 (dysphagia, n = 4; weight loss, n = 1). In contrast, most patients in the cardia cancer group were admitted because of malignant symptoms (dysphagia, n = 26; epigastric pain, n = 9; and anemia, n = 2). Ten of 17 patients in the Barrett esophagus cancer group had tumors limited to the mucosa and submucosa only. In 1 patient the tumor grew into the muscular layer but not through it. In the remaining 6 patients the tumor did grow through the muscular layer and lymph node metastases were found. Wall penetration was found in 30 patients and metastases to lymph nodes in 29 patients in the cardia cancer group. The hospital mortality rate was 0 of 17 patients in the Barrett cancer group and 2 of 37 patients in the cardia cancer group. In the patients operated on for adenocarcinoma in the distal esophagus, a better long-term survival rate was seen in those with Barrett epithelium (50%) than in those without this metaplasia (10%) (log rank P = .005; X2 = 7.80). CONCLUSIONS: Concomitant Barrett epithelium improved the prognosis for patients with adenocarcinoma in the distal esophagus. Probably the reason for this was a higher rate of early-stage disease, because symptoms of gastroesophageal reflux and other benign disorders, not dysphagia, were most common in patients with adenocarcinoma without Barrett epithelium in the distal esophagus.

Adenocarcinoma↗
PubMed1996

Synthetic protein analogues in artificial surfactants.

Today, airway instillation of surfactant preparations is a generally used treatment for respiratory distress syndrome in premature infants. Most commercially available surfactants are purified from animal lungs and contain lipids, mainly phospholipids, and about 2% of the hydrophobic surfactant proteins B and C (SP-B and SP-C). During the last half-decade the main structural properties of these proteins have been clarified and this knowledge now makes it possible to design synthetic analogues for future use in artificial surfactants.

Drug Design↗
PubMed1995

Secondary structure and biophysical activity of synthetic analogues of the pulmonary surfactant polypeptide SP-C.

Native pulmonary-surfactant-associated lipopolypeptide SP-C, its chemically depalmitoylated form and several synthetic analogues lacking the palmitoylcysteine residues were analysed for secondary structure in phospholipid micelles and for biophysical activity in 1,2-dipalmitoyl-sn-glycero-3- phosphocholine/phosphatidylglycerol/palmitic acid (68:22:9, by wt.). Compared with the native molecule, with the entire poly-valyl part in a known alpha-helical conformation, depalmitoylated SP-C was found to be still mainly alpha-helical, but with an approx. 20% decrease in the helical content. A synthetic hybrid polypeptide where the entire poly-valyl alpha-helical part of native SP-C had been replaced with the amino acid sequence of a transmembrane helix of bacteriorhodopsin is also predominantly alpha-helical. In contrast, synthetic SP-C analogues lacking only the palmitoyl groups, by replacement of the palmitoylcysteine residues with cysteine, phenylalanine or serine, or lacking the positively charged amino acids by replacement with alanine, are considerably less alpha-helical than both native and depalmitoylated SP-C. The data indicate that the SP-C palmitoyl groups are important for maintenance of the alpha-helical conformation in parts of the polypeptide, and that the poly-valyl alpha-helical conformation is not fully formed in synthetic SP-C polypeptides. Furthermore, the helical structure of both native and depalmitoylated SP-C in dodecylphosphocholine micelles is very resistant to thermal denaturation, exhibiting ordered structure at 90 degrees C. The alpha-helical content grossly parallels the peptide-induced acceleration of the spreading of phospholipids at an air/water interface and the increase of surface pressure. The data suggest that the alpha-helical conformation itself, rather than just the covalent structure, is of prime importance for the biological function of synthetic pulmonary-surfactant peptides.

Amino Acid Sequence↗
PubMed1995

Structural and functional importance of the C-terminal part of the pulmonary surfactant polypeptide SP-C.

A synthetic non-palmitoylated form of the pulmonary surfactant protein SP-C and three peptides of different lengths corresponding to its N-terminal and middle parts were reconstituted into dipalmitoylglycerophosphocholine/phosphatidylglycerol (7:3, by mass) lipid bilayers. The adsorption properties of each reconstituted system were determined by measurement of the surface pressure after injection of the samples underneath an air/water interface. Attenuated total reflection infrared spectroscopy provided information about the structure and orientation of peptides in lipid bilayers. The hydrophobic C-terminal helix is crucial for the rapid adsorption as shortening of the C-terminal part drastically restricted this activity. The C-terminal amino acid sequence can however be replaced with that of the second transmembrane helix of bacteriorhodopsin without significantly modifying the adsorption properties. The data suggest that the hydrophobic C-terminal part allows the anchorage of SP-C in the lipid bilayer in such a manner that the N-terminal domain adopts an optimal conformation and orientation for the rapid adsorption of phospholipids at the air/water interface, and/or that a membrane-spanning helix as such is needed for this activity.

Adsorption↗
PubMed1995

Pulmonary surfactant-associated polypeptide SP-C in lipid micelles: CD studies of intact SP-C and NMR secondary structure determination of depalmitoyl-SP-C(1-17).

The surfactant-associated polypeptide C (SP-C) is a 35-residue lipopolypeptide which is essential for the function of surfactants used for therapy of infant respiratory distress. Modeling based on the recently determined nuclear magnetic resonance (NMR) structure of native SP-C in an organic solvent showed that SP-C could readily insert into fluid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine bilayers. The present paper describes further physical-chemical studies of intact SP-C and its N-terminal 17-residue polypeptide fragment, depalmitoyl-SP-C(1-17), in the presence of dodecylphosphocholine micelles. The results obtained provide a link between the NMR solution structure and the behaviour of SP-C in an ordered lipid environment, and thus present new insights for rational design of SP-C analogs for therapeutic purposes.

Amino Acid Sequence↗
PubMed1995

An amphipathic helical motif common to tumourolytic polypeptide NK-lysin and pulmonary surfactant polypeptide SP-B.

The tumour-lysing and antimicrobial polypeptide NK-lysin and the pulmonary surfactant-associated polypeptide SP-B exhibit 24% residue identities (49% similarities), including six half-cystine residues in the same disulphide bonding pattern, and similar far-UV circular dichroism spectra corresponding to 45-55% alpha-helix and 20-25% beta-sheet structures. From this, we conclude that the conformations of NK-lysin and SP-B are similar. In contrast, the functional properties of the two proteins are dissimilar: SP-B does not exhibit antibacterial activity and NK-lysin does not significantly effect phospholipid spreading at an air/water interface. Saposins, which solubilize lipids and activate lysosomal hydrolases, the pore-forming amoebapores, and parts of acid sphingomyelinase and acyloxyacylhydrolase, also share 18-27% sequence identities with NK-lysin (and SP-B), including the six conserved half-cystine residues. The inclusion of NK-lysin extends the family of saposin-like polypeptides, all members of which appear to interact with lipids. Strictly conserved structural features with implications for helix topology and lipid interactions are observed.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1995

The effect of environment on the stability of an integral membrane helix: molecular dynamics simulations of surfactant protein C in chloroform, methanol and water.

A series of three molecular dynamics simulations at 300 K in explicit solvent environments of chloroform, methanol and water has been performed on the pulmonary surfactant lipoprotein, SP-C, comprising several consecutive valine residues in order to investigate the stability of the alpha-helical conformation. Two additional simulations were performed on truncated SP-C with a five-residue N-terminal deletion at 300 K and 500 K in water, the high temperature run in order to increase the rate of peptide denaturation. Indications of destabilization appear in chloroform during 1 ns while the SP-C alpha-helix is remarkably stable during 1 ns in methanol and water. In particular the polyvalyl part comprising residues Val15 to Val21 remains intact even at elevated temperature, and the valines do not disrupt the alpha-helical conformation. The valyl-rotamer sampling is partly restricted. Unfolding takes place successively along the primary sequence starting from the C-terminal end. Factors affecting polypeptide stability in molecular dynamics simulations are addressed. The intrinsic helix-forming tendency of valine residues and its dependence on the sequence context, and the role of the solvent environment in stabilizing or destabilizing an alpha-helical fold, are discussed.

Amino Acid Sequence↗
PubMed1995

A model of error propagation in the presence of an error-enhancing drug.

A mathematical model is considered that describes error propagation in protein synthesis, with emphasis on the role of an error-enhancing drug such as streptomycin. The subject of error propagation has been investigated in a number of works since an original proposal by Orgel in 1963. From experiments, it is known that streptomycin given to a bacterium culture in small concentration increases the error level, but at a certain concentration threshold the bacteria die. This two-fold behavior has, in some papers, lead to the proposal that another effect of the drugs besides that of error propagation leads to the death of the bacteria. In the present work, we use a model related to kinetic models of selection in protein synthesis which include the combined effect of ribosome and synthetase action. The model shows very clear threshold effects: for small values of the parameter that represents the drug action, a stable situation is found that has an increased error level but still attains a rather high accuracy. At a certain threshold, this is no longer maintained. The main emphasis here is on the time evolution of relevant parameters, and it is also shown how this can be quite drastic: the accuracy may decrease rather smoothly to a critical point, where it is drastically lost and where the bacteria may die out very suddenly.

Bacteria↗
PubMed1995

A comparison between the effects of gemfibrozil and simvastatin on insulin sensitivity in patients with non-insulin-dependent diabetes mellitus and hyperlipoproteinemia.

In a double-blind, randomized crossover study, 29 patients with non-insulin-dependent diabetes mellitus (NIDDM) and hyperlipoproteinemia were treated with gemfibrozil (1,200 mg/d) or simvastatin (10 mg/d) for 4 months. After gemfibrozil treatment, the insulin concentration was increased during the major part of the intravenous glucose tolerance test (IVGTT) and during the hyperinsulinemic euglycemic clamp. Similar but less pronounced elevations were caused by simvastatin. Insulin sensitivity decreased by 27% and 28% during gemfibrozil and simvastatin treatment, respectively. Low-density lipoprotein (LDL) cholesterol was decreased with simvastatin treatment by 24%. The LDL cholesterol level was not changed by gemfibrozil, but very-low-density lipoprotein (VLDL) cholesterol was reduced by 40%. The VLDL triglyceride concentration was reduced to a significantly greater extent by gemfibrozil. After gemfibrozil treatment, lipoprotein(a) [Lp(a)] was decreased by 24%, and the plasma free fatty acid (FFA) concentration was increased by 20% and skeletal muscle lipoprotein lipase activity (LPLA) by 37%. Although simvastatin more effectively decreased LDL cholesterol levels and the LDL to high-density lipoprotein (HDL) ratio, it cannot be claimed unreservedly that this drug is necessarily preferable in NIDDM patients. Gemfibrozil improved triglyceride removal and decreased VLDL concentrations, with qualitative changes in LDL. The apparent effects on insulin sensitivity are difficult to evaluate and need further study.

Aged↗