Biomedical subjects

J Johansson

Publications and source records attributed to J Johansson.

At least 163 records · Page 9Linked to original sources

PubMed1993

NMR determination of the secondary structure and the three-dimensional polypeptide backbone fold of the human sterol carrier protein 2.

Nuclear magnetic resonance (NMR) spectroscopy was used to determine the secondary structure and the three-dimensional polypeptide backbone fold of the human sterol carrier protein 2 (hSCP2), which is a basic protein with 123 residues believed to participate in the intracellular transport of cholesterol and various other lipids. Sequence-specific assignments were obtained for nearly all backbone 1H and 15N resonances, as well as for about two-thirds of the side-chain 1H resonances, using uniform 15N-labeling of the protein combined with homonuclear two-dimensional 1H NMR and three-dimensional 15N-correlated 1H NMR. Three alpha-helices comprising the polypeptide segments of residues 9-22, 25-30 and 78-84 were identified by sequential and medium-range nuclear Overhauser effects (NOE). The analysis of long-range backbone-backbone NOEs showed that hSCP2 further contains a five-stranded beta-sheet including the residues 33-41, 47-54, 60-62, 71-76 and 100-102, which is a central feature of the molecular architecture. The first three strands are arranged in an antiparallel fashion, the polypeptide chain then crosses over this three-stranded sheet in a right-handed sense so that the fourth strand is added parallel to the first one. The fifth strand runs antiparallel to the fourth one, so that the overall topology is +1, +1, -3x, -1. The three-dimensional arrangement of the beta-sheet and the first two helices was determined using an input of 625 NOE upper distance constraints and 95 scalar coupling constants for a preliminary structure calculation with the distance geometry program DIANA.

Amino Acid Sequence↗

PubMed1993

The role of lipids and antioxidative factors for development of atherosclerosis. The Probucol Quantitative Regression Swedish Trial (PQRST).

The effect of probucol on the development of atherosclerosis is being investigated in the Probucol Quantitative Regression Swedish Trial (PQRST). Hypercholesterolemic patients are randomized to receive either probucol 0.5 g twice daily or placebo in a double-blind manner, in combination with dietary therapy and cholestyramine 8-16 g daily for a 3-year period. The primary endpoint of the trial is the change in atheroma volume, assessed by annual quantitative angiography involving 20-cm segments of the femoral artery. Data from the open diet and prerandomization phase indicate that probucol added to dietary intervention plus cholestyramine produced highly significant reductions in total (-17%), low-density lipoprotein (LDL; -10%), and high-density lipoprotein (-30%) cholesterol. From a subpopulation, LDL levels were isolated during different stages of the prerandomization phase. LDL was exposed to the oxidant Cu2+ and binding to fibroblasts as well as degradation by macrophages was measured. The generation of thiobarbituric acid-reactive substances (TBARS) was also measured. Probucol prevented degradation of copper-exposed LDL by macrophages and also reduced the formation of TBARS, indicating that probucol protected LDL from oxidation. After the trial concludes in December 1992, statistical models will be used to investigate how much of the change in atherosclerosis is explained by changes in lipoprotein concentrations and how much is explained by probucol's antioxidative effects. Thus, other metabolic factors such as dietary intake and circulating levels of lipid soluble vitamins and fatty acids that may modify the possible antioxidative effects of probucol are also measured and will be related to change in atherosclerosis.

Aged↗

PubMed1993

Primary sensory afferents in the thymus of the guinea pig demonstrated with anterogradely transported horseradish peroxidase conjugates.

After injections of wheat germ agglutinin- or B-subunit of cholera toxin-horseradish peroxidase (HRP) conjugates into the C2-C4 dorsal root ganglia of the guinea pig and anterograde axonal transport of the conjugates, labeled nerve fibers were found in the thymus mainly on the ipsilateral side. The distribution of the HRP-labeled fibers was similar to that of nerves immunoreactive to substance P and calcitonin gene-related peptide, which were partly colocalized. The results show that the thymus is innervated by primary sensory afferents which have their cell bodies in dorsal root ganglia.

Afferent Pathways↗

PubMed1993

Outcome 5 years after 360 degree fundoplication for gastro-oesophageal reflux disease.

Forty patients with a mean age of 45 (range 22-65) years were operated on between 1982 and 1985 for gastro-oesophageal reflux disease with a short floppy 360 degree fundoplication. The results of the operation were determined by endoscopy, oesophageal manometry, ambulatory 24-h pH recording and symptom evaluation 6 months and 5 years after operation. These results were compared with findings in healthy controls. The median pressure in the lower oesophageal high-pressure zone was 13.3 (interquartile range (i.q.r.) 11.3-21.3) mmHg after 5 years, which did not differ significantly from the value at 6 months' follow-up or from that in controls. It was, however, significantly higher than the preoperative pressure. The median intra-abdominal length of the high-pressure zone was 1.7 (i.q.r. 1.3-2.3) cm after 5 years, significantly less than at 6 months but equal to control length. Measurement of the proportion of total time at pH < 4 at 5 years (median 0.2 (i.q.r. 0.0-0.6) per cent) and 6 months after operation revealed a significant reduction in acid reflux compared with preoperative values and normal controls. There was no significant difference in acid exposure between the two postoperative investigations. Endoscopy showed that 27 patients had no oesophagitis, three had erythema and three persistent Barrett's oesophagus 5 years after operation. Normal belching was possible in 22 patients and 18 experienced increased flatulence 5 years after fundoplication. An independent gastroenterologist found that the result was excellent in 16 patients, good in 16 and fair in four; two patients had a poor overall outcome of the operation. It is concluded that a 360 degree fundoplication provides good long-term control of reflux and that slight symptoms of overcompetence are common among patients operated on without affecting the overall result.

Adult↗

PubMed1993

Clinical fluorescence diagnosis of human bladder carcinoma following low-dose Photofrin injection.

A point-monitoring fluorescence diagnostic system based on a low-energy pulsed laser, fiber transmission optics, and an optical multichannel analyzer was used for diagnosis of patients with bladder malignancies. Twenty-four patients with bladder carcinoma, carcinoma in situ, and/or dysplasia were injected with hematoporphyrin derivative, Photofrin, 0.35 or 0.5 mg/kg body weight, forty-eight hours prior to the investigation. The ratio between the red sensitizer emission and the bluish tissue autofluorescence provided excellent demarcation between papillary tumors and normal bladder wall. Certain cases of dysplasia also could be differentiated from normal mucosa. Benign exophytic lesions such as malakoplakia appeared different from malignant tumors in fluorescence. Flat suspicious bladder mucosa such as seen in infectious diseases or after radiation therapy appeared normal on fluorescence.

Adult↗

PubMed1993

Laser-induced fluorescence in malignant and normal tissue of rats injected with benzoporphyrin derivative.

Laser-induced fluorescence was used to characterize the localization of intravenously administered benzoporphyrin derivative-monoacid (BPD-MA) 3 h postinjection in different rat tissue types, including an induced experimental malignant tumor. A comparison of the fluorescence properties and demarcation potential between the newer sensitizer BPD-MA and four other substances, hematoporphyrin (HP), polyhematoporphyrin ester (PHE), tetrasulfonated phthalocyanine (TSPc) and the commercially available Photofrin earlier investigated, is included. The fluorescence light was induced with a nitrogen laser, emitting at 337 nm. The fluorescence spectrum in the region 380-750 nm was analyzed by a polychromator equipped with a diode array detector. The demarcation potential between tumor and surrounding tissue in terms of fluorescence signal for the tumor model used was 2:1 for BPD-MA. In comparison with the other drugs, HP shows about the same demarcation potential, whereas Photofrin and PHE exhibit about 3 times better and TSPc about 1.5 times better demarcation. By also employing the endogenous tissue fluorescence signature the contrast was enhanced by a factor of about 2 for each of the five drugs.

Animals↗

PubMed1993

Serum lipoproteins and hemostatic function in intermittent claudication.

Normoglucemic men with intermittent claudication (n = 41), mean age of 63 years, and sex-, age-, body mass index-, and smoking habit-matched controls (n = 75) were compared for plasma lipoprotein and hemostatic variables. The patients had significantly lower levels of large high-density lipoprotein (HDL) particles (HDL2b, HDL2a, and HDL3a) and elevated lipoprotein(a) [Lp(a)] concentrations than the control subjects. Of the hemostatic variables, plasminogen activator inhibitor-1 (PAI-1), plasma antiplasmin, plasma fibrinogen, and urine beta-thromboglobulin concentrations were significantly elevated in patients. In intermittent claudication patients Lp(a) correlated significantly with activation of the coagulation system, ie, with the levels of plasma fibrinogen and urine fibrinopeptide A. No correlations between the values for Lp(a) and PAI-1 or plasma alpha 2-antiplasmin were seen. The PAI-1 activity showed significant univariate correlations to the levels of HDL3b, HDL2b (inverse), and very-low-density lipoprotein triglycerides, of which the positive correlation to HDL3b persisted in multivariate analysis (r = .48, P < .001). Independent characteristics for intermittent claudication estimated by multiple regression analysis were PAI-1, plasma fibrinogen, and HDL3a, with a combined R2 of .36. The intermittent claudication subgroup that was being treated with beta-blockers/thiazides had a higher frequency of coronary heart disease compared with the other patients. In addition, the patients taking beta-blockers/thiazides had elevated triglyceride concentrations, lower HDL cholesterol with a size shift toward smaller particles, and a tendency toward raised PAI-1 and plasma alpha 2-antiplasmin levels compared with the patient group that did not take these medications.

Blood Coagulation↗

PubMed1993

Selective salpingography and fluoroscopic transcervical salpingoplasty for diagnosis and treatment of proximal fallopian tube occlusions.

In 25 women with primary or secondary infertility, primary hysterosalpingography (HSG) or laparoscopy with chromopertubation indicated 33 proximal and 2 distal tubal obstructions. Four salpingectomies had been performed earlier. All patients were considered for transcervical catheter salpingoplasty (TCSP) to reconstruct tubal patency. Secondary examination with repeat HSG or selective osteal salpingography confirmed 26 proximal and 3 distal tubal occlusions while 17 tubes were patent. Selective osteal salpingography was performed successfully in 32 of 33 (97%) tubes. Sixteen of 26 (61.5%) proximally occluded tubes were successfully recanalized by coaxial catheter and guidewire technique while two of three distally occluded tubes were reopened by forceful flushing of contrast medium. So far, one ectopic and five intrauterine pregnancies were achieved in ten patients with observation time more than four months. Three patients have had normal deliveries. The favorable results, lack of complications and low costs seem to justify the recommendation to use selective salpingography and fallopian tube recanalization as the first intervention in patients with obstruction of the proximal fallopian tube.

Adult↗

PubMed1993

Reproducibility of quantitative arteriographic assessment of atherosclerosis in the femoral artery.

Results from computer-analysed angiograms in the Probucol Quantitative Regression Swedish Trial (PQRST) were analysed to determine the reproducibility of the method and any drift in the analysing system. The precision index (P(mu)) for 2 angiography series, made at 10 min intervals, of the femoral artery in 276 patients was 10.5 for lumen volume and 21.9 for roughness (edge irregularity). No difference in reproducibility was found between patients with and without symptoms of peripheral atherosclerosis or when looking at the reproducibility over years. A drift of 0.67% per year in the radiographic equipment (but not in the analysis system) was found, confirmed by use of phantoms. Computer-based analysis of femoral atherosclerosis is a reliable method for follow-up trials, giving high reproducibility even if the trial spans over several years and involves different centres. The use of phantoms is essential for checking the method over time.

Adult↗

PubMed1992

Secondary structure and orientation of the surfactant protein SP-B in a lipid environment. A Fourier transform infrared spectroscopy study.

Attenuated total reflection Fourier transform infrared spectroscopy was used to investigate the secondary structure of the surfactant protein SP-B. Nearly half of the polypeptide chain is folded in an alpha-helical conformation. No significant change of the secondary structure content was observed when the protein is associated to a lipid bilayer of dipalmitoylphosphatidylcholine (DPPC)/phosphatidylglycerol (PG) or of dipalmitoylphosphatidylglycerol (DPPG). The parameters related to the gamma w(CH2) vibration of the saturated acyl chains reveal no modification of the conformation or orientation of the lipids in the presence of SP-B. A model of orientation of the protein at the lipid/water interface is proposed. In this model, electrostatic interactions between charged residues of SP-B and polar headgroups of PG, and the presence of small hydrophobic alpha-helical peptide stretches slightly inside the bilayers, would maintain SP-B at the membrane surface.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1992

Cysteine reactivity in sorbitol and aldehyde dehydrogenases. Differences towards the pattern in alcohol dehydrogenase.

In sorbitol dehydrogenase only one cysteine residue, Cys-43, is reactive in both anionic buffer (phosphate) and zinc-liganding buffer (imidazole) upon carboxymethylation. This is in contrast to the situation in the structurally related liver alcohol dehydrogenase, with either of two alternative Cys residues being reactive, and is compatible with differences in zinc-binding and active site relationships between these two metalloenzymes. Unrelated aldehyde dehydrogenase, upon carboxamidomethylation, shows a third pattern, now less well defined but confirming the presence of a thiol function of Cys-302 close to the active site.

Alcohol Dehydrogenase↗

PubMed1992

Human surfactant polypeptide SP-B. Disulfide bridges, C-terminal end, and peptide analysis of the airway form.

Human hydrophobic surfactant polypeptide, SP-B, purified from lung tissue by exclusion chromatography in organic solvents, has been characterized. The polypeptide is 79 residues long, has a C-terminal methionine, and contains seven Cys residues. Native human SP-B lacks free thiol groups. Three intrachain disulfide bridges were defined, linking Cys8 to Cys77, Cys11 to Cys71 and Cys35 to Cys46. The remaining Cys48 is concluded to link the protein chains into homodimers via an interchain disulfide to its counterpart in a second SP-B polypeptide. These SS bridges are identical to those in the porcine form and confirm a consestant and unique disulfide pattern for SP-B polypeptides in general.

Amino Acid Sequence↗

PubMed1992

Identification of hydrophobic fragments of alpha 1-antitrypsin and C1 protease inhibitor in human bile, plasma and spleen.

Hydrophobic peptides were isolated from the phospholipid fraction of human bile, plasma and spleen by exclusion chromatography in organic solvents. From plasma, the activation peptide of C1 protease inhibitor was recovered, from spleen the activation peptide of alpha 1-antitrypsin, and from bile, both these peptides, as well as a fragment generated by proteolytic cleavage of alpha 1-antitrypsin six residues N-terminal of the P1-P1' peptide bond. Cleavages in this region inactivate antiproteases but have previously not been reported to occur in vivo. These peptides in human bile may reflect physiological actions in regulation of antiproteolytic activity or bile secretion processes, and/or be of importance for the physicochemical state of cholesterol, phospholipids and bile acids in bile.

Bile↗

PubMed1992

Structure and orientation of the surfactant-associated protein C in a lipid bilayer.

The secondary structure of native and depalmitoylated porcine surfactant-associated protein C (SP-C) was studied by attenuated total reflection Fourier-transform infrared spectroscopy. Both forms of porcine SP-C adopt mainly an alpha-helical conformation. These two forms of the protein were reconstituted in a lipid bilayer. The insertion of the protein in a membrane is associated with an increase of the alpha-helical content. Dichroic measurements show that, in both cases, the long axis of the alpha-helix is oriented parallel to the lipid acyl chains.

Animals↗

PubMed1992

Splenic primary sensory afferents in the guinea pig demonstrated with anterogradely transported wheat-germ agglutinin conjugated to horseradish peroxidase.

The distribution of primary visceral afferents to the spleen of the guinea pig was studied after injections of wheat-germ agglutinin conjugated to horseradish peroxidase (HRP) into the left dorsal root ganglia at levels T7-T12. After anterograde transport of the tracer, labeled fibers were found in the nerves around the splenic artery in the hilus region and in the splenic parenchyma. The majority of labeled fibers in the spleen were detected in the white pulp. HRP-positive fibers were also observed in the red pulp and in the trabeculae. The distribution of the HRP-labeled fibers was in part similar to those of substance P-immunoreactive and calcitonin gene-related peptide-immunoreactive nerve structures. The results show that the anterograde tracing technique can be used successfully to investigate splenic primary afferent innervation.

Afferent Pathways↗

PubMed1992

Work environment functions in small enterprises in Sweden.

In Sweden, a governmental commission has formed new strategies concerning the work environment with the aims of reducing employee absenteeism and re-employing those individuals who have already left employment as a result of bad working conditions. The main features in this new approach are: strengthening of the legislation; a responsibility for work injury costs; and a distinct rehabilitation responsibility. In this paper the authors discuss how these proposals suited the constraints and facilities of small enterprises, employing less than 50 persons. The results are based on interviews carried out with company directors, safety representatives and labour inspectors. The interviews revealed that the company directors had a negative attitude towards both the strengthening of legislation and responsibility for work injury costs. It was also revealed that the small companies lack both knowledge of how a good environment can be created and the state of their own work environment. It seems that the small companies cannot handle work environment questions in a systematic way without comprehensive education and training or without seeking expert assistance outside the company.

Journal Article↗

PubMed1992

Close correlation between high-density lipoprotein and triglycerides in normotriglyceridaemia.

The relationship between high-density-lipoprotein (HDL) particle size subclasses and the levels of the major lipoprotein lipids was studied in 74 men consecutively referred to the lipid clinic. HDL (density 1.070-1.21 kg l-1) was separated by polyacrylamide gradient gel electrophoresis (GGE) into five size-defined subclasses, in order of decreasing size as follows: HDL2b, HDL2a, HDL3a, HDL3b and HDL3c. Cholesterol and triglyceride concentrations in very-low-density (VLDL), low-density (LDL) and high-density (HDL) lipoproteins were determined. The level of VLDL triglycerides was negatively correlated with HDL2b (r = -0.66, P less than 0.0001), and positively correlated with HDL3b concentrations (r = 0.65, P less than 0.0001). Both correlations were restricted to subjects with VLDL triglyceride concentrations of less than 1.80 mmol l-1, i.e. those with normotriglyceridaemia. Patients with a history of myocardial infarction and/or angina pectoris (n = 18) had significantly lower HDL2b levels than subjects with asymptomatic hyperlipidaemia (n = 50), i.e. 0.16 vs. 0.22 mg protein ml-1 (P less than 0.05), despite essentially similar cholesterol and triglyceride levels in the VLDL, LDL and HDL fractions, including HDL2 and HDL3 cholesterol.

Adult↗

PubMed1992

Correlation between computer-assisted femoral arteriography and physiological tests in hypercholesterolaemic patients: a methodological study with special reference to clinical trials.

The validity of computer-assisted femoral arteriography, for the study of regression/progression of atherosclerosis in follow-up clinical trials, was investigated by comparison with routine physiological estimates of peripheral circulatory function. Thus, in 114 hypercholesterolaemic patients, the results of aorto-femoral arteriography were compared with those of leg segmental blood pressure measurement, oscillometry, digital pulse plethysmography, and bicycle and treadmill exercise tests. In 107 patients, 18 with symptoms of peripheral vascular disease (PVD) and 89 asymptomatic, magnification arteriograms of a 20 cm segment of the right or left superficial femoral artery were obtained. These arteriograms were digitized and the following variables were calculated: arterial lumen volume (corrected for body size), per cent stenosis, and edge roughness. The correlation between arteriographic and physiological variables was investigated with a linear regression model, taking into account the possible interaction with sex, and presence or absence of symptoms of PVD. Lumen volume correlated significantly with all five physiological variables, and per cent stenosis correlated significantly with four of the physiological variables. For the roughness measure, however a significant correlation was found only with plethysmography. By using logistic multiple regression analysis linear functions of physiological variables were constructed to detect ilio-femoral arterial occlusion. The sensitivity/specificity for detection of right-sided, left-sided, and bilateral occlusion was 0.83/0.98, 0.78/0.98, and 0.60/1.00 respectively (N = 108-111). Systolic blood pressure (ankle-arm ratio) was the single variable most closely correlated to the likelihood of arterial occlusions. It is concluded that arterial lumen volume and per cent stenosis, measured for the digitized femoral arteriogram, correlate well with physiological variables, which reflect the state of atherosclerosis both in the femoral arteries and in other arterial beds including the heart, and that routine physiological tests can be used to identify patients with arterial occlusions in the iliac and femoral arteries.

Adult↗