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Biomedical subjects

J Johansson

Publications and source records attributed to J Johansson.

At least 199 records · Page 11Linked to original sources

Development of femoral atherosclerosis in hypercholesterolemic patients during treatment with cholestyramine and probucol/placebo: Probucol Quantitative Regression Swedish Trial (PQRST): a status report.

The Probucol Quantitative Regression Swedish Trial is being performed to investigate the effects of probucol on atherosclerosis in the femoral artery. Probucol is combined with cholestyramine and dietary management in hypercholesterolemic patients, and the effects of atheroma developing in the femoral artery will be followed by a quantitative angiographic technique. A randomly selected control group is also being managed by dietary therapy and cholestyramine, but receives placebo instead of probucol. The treatment time in this double-blind trial is 3 years, and femoral angiography is performed yearly. Detailed lipoprotein and apolipoprotein analysis are performed at monthly intervals. The basic study design is described here, and some results from the open prerandomization phase of the study are presented.

Arteriosclerosis↗

Size and structure of the hydrophobic low molecular weight surfactant-associated polypeptide.

The most abundant low molecular weight protein of pulmonary surfactant has unusual properties. Its primary structure has now been determined by analysis at the protein level. The highly hydrophobic polypeptide is resistant to cleavage with proteolytic enzymes, but it was possible to generate fragments by limited cleavage with concentrated HCl or with sodium in liquid ammonia. Acid hydrolysis of the peptide required exceptional conditions for release of all residues. The N-terminus is heterogeneous, and in its longest form the primary structure consists of 35 residues. This analysis establishes that the size of the major native hydrophobic surfactant polypeptide is considerably smaller than previously proposed. Biological effects of the polypeptide recombined with phospholipids are confirmed in vitro by using a pulsating bubble system and in vivo by using premature newborn rabbits. The molecule has branched-chain amino acid residues at about two-thirds of all positions and lacks nine types of residue. The middle third is composed entirely of hydrophobic residues, and fragments from this part are sparingly soluble even in organic solvents. The hydrophobic region is preceded by a more hydrophilic, N-terminal segment. Thus, the molecule has two contrasting parts, like a detergent, which may explain its essential role in the pulmonary surfactant system.

Amino Acid Sequence↗

Hydrophobic 3.7 kDa surfactant polypeptide: structural characterization of the human and bovine forms.

The human and bovine forms of the hydrophobic 3.7 kDa surfactant polypeptide have been structurally analyzed. The polypeptide is essentially inert to enzymatic proteolysis, and methods for analysis include peptide handling in organic solvents and fragment generation by limited acid hydrolysis. The molecule exhibits N-terminal trimming, and the relative abundance of the different starting positions varies both among species and between adult and fetal forms of the surfactant polypeptide. The bovine major form is one residue shorter than the mature 35-residue human molecule. Comparison of the porcine, human and bovine polypeptides reveals a conserved hydrophobic middle/C-terminal segment and a variable hydrophilic N-terminal part.

Amino Acid Sequence↗

Low-molecular-mass surfactant protein type 1. The primary structure of a hydrophobic 8-kDa polypeptide with eight half-cystine residues.

The low-molecular-mass surfactant protein fraction, soluble in chloroform/methanol, contains at least two separate polypeptide chains. The 8-kDa form (type I) was isolated, [14C]carboxymethylated after reduction, and submitted to structural analysis. Its highly hydrophobic nature complicated purification, proteolytic cleavages, and sequence analysis. Acid hydrolysis in 6 M HCl for 7 days was necessary for release of branched-chain residues in full yield. Pepsin was the only enzyme found to cleave the surfactant protein and was used to complement peptide generation by chemical cleavage with CNBr. The primary structure deduced consists of 79 residues with 8 half-cystine residues, and a total of 39% branched-chain hydrophobic residues. However, 11 residues are charged at physiological pH, and all properties of the primary structure are not entirely outstanding in relation to those of other proteins. Hydrophobic segments, coupled with a presumably tight folding from the presence of disulfide bridges, probably explain the unusual properties and the solubility in organic solvents.

Amino Acid Sequence↗

Mitochondrial aldehyde dehydrogenase from horse liver. Correlations of the same species variants for both the cytosolic and the mitochondrial forms of an enzyme.

The primary structure of the mitochondrial form of horse liver aldehyde dehydrogenase has been determined, utilizing peptide analyses and homology with other enzyme forms. The subunit exhibits N-terminal heterogeneity in size similar to that for the corresponding human mitochondrial protein, the longest form having 500 residues. Catalase was identified as a contaminant of the preparations. All four pairs within a set of aldehyde dehydrogenases can now be compared, including the same two species variants (horse and human) for both the cytosolic and mitochondrial enzyme, revealing characteristic differences although Cys-302 and other segments of presumed functional importance are unchanged. The cytosolic and mitochondrial enzymes are clearly different (172 exchanges in the horse pair; 160 exchanges in the human pair) and the mitochondrial forms are more conserved (28 exchanges of 500 residues) than the cytosolic ones (43 exchanges). Distributions of the residue substitutions also differ between the two enzyme types. These results suggest a comparatively distant separation of the cytosolic and mitochondrial enzymes into forms with separate functional constraints that are more strict on the mitochondrial than the cytosolic enzyme. Unexpectedly, positions with residues unique to one of the four enzymes are about twice as common in both of the horse proteins than in either of the human proteins. This difference may reflect a general pattern for human/non-human proteins, showing that not only functional properties of the protein, but also other factors, such as generation time (longer in man than in horse), are important for enzyme divergence.

Aldehyde Dehydrogenase↗

Calf muscle adaptation in intermittent claudication. Side-differences in muscle metabolic characteristics in patients with unilateral arterial disease.

The adaptation of enzyme activities, notably in the oxidative metabolism, and of prerequisites for tissue transport of oxygen in the claudication leg was evaluated by comparing muscle biopsies from the gastrocnemius muscle of the claudication and the symptom-free leg of seven patients with unilateral claudication. The claudication leg had higher activities of a marker enzyme for mitochondrial oxidative capacity, citrate synthase (CS), as well as of the MB and the mitochondrial isoenzyme of creatine kinase (CK), which are considered to be involved in the transfer of high energy phosphate from the mitochondria to the resynthesis of ATP in the cytoplasm. The difference between claudication and healthy leg in activities of these CK isoenzymes were well correlated with the corresponding side difference in CS activity. No significant differences between claudication and healthy leg were found in distribution of muscle fibre types or fibre dimension, capillary density or myoglobin content, nor was there any side difference in phosphofructokinase or lactate dehydrogenase. Side differences tended to be greater in those patients with the most advanced obstructive arterial disease as estimated from non-invasive pressure measurements. It is concluded that in reasonably physically-active patients, the mode of ischaemia to which the claudication leg is subjected leads to a metabolic adaptation characterized by increased activities of enzymes involved in the oxidative metabolism, but no significant adaptation of either the conditions for local oxygen transport, as estimated by myoglobin content, and capillary density, or capacity for anaerobic metabolism.

Aged↗

Topical non-steroidal anti-inflammatory drugs inhibit non-immunologic immediate contact reactions.

The effects of 3 topical applications of non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac 1%, naproxene 10% and salicylic acid 5% in gel vehicles, on immediate contact reactions to 500 mM benzoic acid, 500 mM cinnamic aldehyde, 50 mM methyl nicotinate, all in pet., and 14.1 M (100%) dimethyl sulfoxide, were studied in 16 medical students. Erythema and edema reactions were observed visually, and the changes in the skin blood flow were monitored using laser-Doppler flowmetry (LDF). NSAIDs had significant inhibitory effects on erythema induced by all 4 substances tested and on edema induced by methyl nicotinate. The inhibition was probably due in part to percutaneous absorption and systemic effects of NSAIDs. There were differences between visual and LDF assessments, which stresses the importance of monitoring erythematous reactions of the skin both visually and with LDF.

Acrolein↗

Tobacco smoke removal with room air cleaners.

The ability of room air cleaners to remove gases and particles from air contaminated with tobacco smoke has been studied. Thirty-one air cleaners were tested. Various air-cleaning devices were used, ie, electrostatic precipitators, electret fiber filters, ionizers, activated carbon, impregnated alumina, ionizing lamps, and an electron generator. The airflow rates were in the range of 0-500 m3/h. The measurements covered particle sizes of 0.01-7.5 microns and the following gases: carbon monoxide, ammonia, formaldehyde, nitric oxide, nitrogen dioxide, hydrocarbons, and hydrogen cyanide. No formal standard procedure exists for testing room air cleaners; therefore the tests were made in the following way. Tobacco smoke was generated and mixed in a closed room. The room air cleaner was started, and the decay rates for the gases and particles were measured. The results were calculated as equivalent airflow rates, ie, the clean airflow rate causing the same decay rate for contaminant concentrations in a room. The equivalent airflow rates were 0-360 m3/h. The rate of ozone emission by electrostatic precipitators and ionizers was also measured. One general conclusion was that it is much more difficult to remove gases than particles.

Air Conditioning↗

Lipid bilayer polypeptide interactions studied by molecular dynamics simulation.

A model membrane with a polypeptide alpha-helix inserted has been simulated by molecular dynamics at a temperature well above the gel/liquid crystalline phase transition temperature. Order parameters of the lipids and other equilibrium and dynamic quantities have been calculated. Three systems, polyglycine constrained into an alpha-helical configuration, glycophorin with similarly conformationally constrained backbone and finally glycophorin free to change its backbone conformation, have been studied. In all cases there was an ordering of the chains close to the helix. This effect was, however, much smaller for glycophorin with its rather bulky side chains than for polyglycine. The dynamics of the lipids were affected by the neighbouring helix, not drastically however. Lateral diffusion and reorientational time correlations of lipids close to the helix were slower than for the bulk ones, but not more than two or three times. Thus, we did not find any evidence of bound or frozen boundary lipids.

Glycophorins↗

Peptides of postulated inhibin activity. Lack of in vitro inhibin activity of a 94-residue peptide isolated from human seminal plasma, and of a synthetic replicate of its C-terminal 28-residue segment.

A 94-residue polypeptide isolated from human seminal plasma and its chemically synthesized C-terminal 28-residue segment were studied in an in vitro inhibin bioassay utilizing rat pituitary cell cultures. Both peptides have previously been claimed to have inhibin activities, and the effects on the secretion and cellular content of gonadotrophins (FSH and LH) were now assessed in the in vitro assay. No inhibition was found. After 72 h of culture, both the cellular content and the spontaneous as well as the LHRH-stimulated release of bioactive or immunoactive FSH and LH remained unaffected. Similarly, no effects were found on the storage and/or release of prolactin, growth hormone, or thyrotropin. We conclude that both the native 94-residue peptide and the synthetic replicate of its C-terminal 28-residue segment, do not influence the pituitary FSH secretion when assessed in this in vitro system.

Animals↗

Results of surgical treatment for iliofemoral venous thrombosis.

The long-term results after venous thrombectomy combined with a temporary arteriovenous fistula were evaluated in 19 patients. Clinical status, isotope phlebography, venous occlusion plethysmography and foot volumetry were performed after a mean follow-up time of 38 months (range 13-75). The primary operation was successful in 17 of the 19 patients; the 2 remaining had chronic occlusions of their iliac veins. At the time of closure of the arteriovenous fistula, i.e. 3 months after thrombectomy, 14 patients had a patent iliac vein. At follow-up eight patients were considered to have a patent iliac vein, eight had a partial restitution and three had an occluded iliac vein. The group as a whole had no impaired venous emptying of the leg, but the small group of patients with occlusion at follow-up according to isotope phlebography seemed to have an impaired venous emptying. Foot volumetry showed only minor signs of valvular insufficiency, mainly in limbs with distal extension of the initial thrombus or only partial restitution of venous patency. A good long-term result can be expected after venous thrombectomy with a temporary arteriovenous fistula particularly in younger patients where the thrombosis is limited to the iliofemoral segment. This emphasizes the importance of early operation before distal extension of the thrombus occurs.

Adolescent↗

Superoxide dismutase in human testis preparations.

A protein fraction from human testis was structurally investigated. The main component of the fraction reported to contain inhibin-like activity was purified and analyzed by tryptic digestion. The peptides obtained identified the protein as an enzyme, superoxide dismutase, previously known to be present in seminal plasma. The results show that superoxide dismutase is a major enzyme, also of testicular material. They further demonstrate the importance of using pure fractions, and controls such as checks with structural analysis or synthetic peptides, in the work of elucidating the nature of inhibin and other hormonal peptides.

Amino Acid Sequence↗