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Biomedical subjects

A Salminen

Publications and source records attributed to A Salminen.

At least 91 records · Page 5Linked to original sources

Phosphomannosyl receptors of lysosomal enzymes of skeletal muscle in neuromuscular diseases.

The phosphomannosyl receptor system is responsible for both the receptor-mediated endocytosis and the intracellular transport of lysosomal enzymes. In the present study this receptor system was examined in affected muscles of patients with various neuromuscular diseases. The total activity of beta-N-acetyl-glucosaminidase, a marker enzyme of lysosomal hydrolases, was significantly elevated in the patients with myopathies (polymyositis and muscular dystrophies) but only slightly increased in those with neurogenic muscle atrophies (amyotrophic lateral sclerosis, polyneuropathy or other neurogenic muscle disease). The increase was most prominent in the group of polymyositis. The content of phosphomannosyl receptors was increased in the patients with myogenic muscle disease but not in those with neurogenic disease. The receptor binding of lysosomal enzymes was saturable and inhibited with mannose 6-phosphate showing the typical characteristics of phosphomannosyl receptors. The characteristics of the receptors were very similar both to control and to diseased muscle samples. When surveying all the material, the content of phosphomannosyl receptors correlated highly significantly with the muscular activity of beta-N-acetylglucosaminidase, muscle atrophy index, and serum creatine kinase activity.

Adolescent↗

A ras-like protein is required for a post-Golgi event in yeast secretion.

Secretion is blocked at the post-Golgi stage within 5 min of a shift of sec4-8 cells from 25 degrees C to 37 degrees C. Analysis of SEC4 predicts a protein product of 23.5 kd molecular weight that shares 32% homology with ras proteins and is essential for growth. The regions of best homology are those involved in the binding and hydrolysis of GTP. Duplication of SEC4 suppresses post-Golgi-blocked mutations in three sec genes. These mutations are lethal when combined with sec4-8 at 25 degrees C. Mutations that block elsewhere on the pathway are not suppressed by the SEC4 duplication and are not lethal when combined with sec4-8. We propose that the SEC4 product is a GTP-binding protein that plays an essential role in controlling a late stage of the secretory pathway.

Amino Acid Sequence↗

Effects of free fatty acids, lysophosphatides and phospholipase treatment on lipid peroxidation of myocardial homogenates and membrane fractions.

The effects of various free fatty acids, lysophosphatides and phospholipase treatments on the enzymatic and the non-enzymatic lipid peroxidation capacities in the heart homogenates and subcellular fractions were studied. The results showed a dose related inhibition of both the enzymatic and non-enzymatic lipid peroxidation with free fatty acids. A significant inhibition occurred as early as at the concentration of 25-50 microM of several fatty acids both in homogenates and in organelle fractions. In general, the inhibition was greatest with cis-unsaturated, long-chain fatty acids. The inhibition was also induced by the pretreatment of the homogenates with phospholipase A2 but not with phospholipase C. The lysophosphatidyl cholines (16:0 and 18:1) had a stimulatory effect on the enzymatic lipid peroxidation capacity at the physiological concentrations. The results show that the stimulatory/inhibitory effect of various lipid amphiphiles on lipid peroxidation is strongly structure linked and the mitochondrial fraction is the most susceptible to the injury induced by lipid amphiphiles.

Animals↗

Protective effect of indomethacin against exercise-induced injuries in mouse skeletal muscle fibers.

The role of prostaglandin synthesis was evaluated by indomethacin administration in the pathogenesis of exercise-induced muscle fiber injuries in soleus and quadriceps femoris muscles of mice. The administration of indomethacin before, during, and after 9 h exertion (s.c., 6 mg/kg during and just after exertion and 1.5-3 mg/kg before exertion and later twice a day) caused a significant histologic protection against exercise injuries and considerably reduced the exercise responses of beta-glucuronidase and glucose-6-phosphate dehydrogenase activities (enzymatic indicators of necrotic lesions in skeletal muscles) on the 2nd post-exercise day. The administration of indomethacin before and during the exertion (3 and 10 mg/kg, respectively) but not after exertion caused only a slight histologic protection while the enzymatic indicators showed a nonsignificant effect.

Animals↗

Chronic hydrogen peroxide intake and peroxide metabolizing enzyme activities in some tissues of mice and rats.

Chronic daily intake of 0.5% H2O2 in drinking water decreased Se-dependent glutathione peroxidase (Se-GSHPx) activity in rat skeletal muscle, kidney and liver. Non-Se GSHPx activity decreased in kidney. Deprivation of drinking water decreased Se-GSHPx activity in kidney and non-Se GSHPx activity in kidney and liver. H2O2 intake decreased activity of catalase in rat skeletal muscle. H2O2 intake or water deprivation caused no changes in these enzyme activities in mice.

Animals↗

Tularemia in otolaryngologic practice. An analysis of 127 cases.

Ulceroglandular, glandular, and oropharyngeal forms of tularemia may occur in otolaryngologic patients, frequently causing diagnostic difficulties. A retrospective analysis of 127 patients with serologically proved tularemia in the head and neck region is presented with special reference to diagnostic difficulties. Short case reports of six patients are included. Difficulties seemed to appear especially in the diagnosis of glandular tularemia. Oropharyngeal tularemia is easily confused with infectious mononucleosis. A high degree of suspicion of tularemia is recommended in endemic areas.

Adolescent↗

Collagen metabolism of mouse skeletal muscle during the repair of exercise injuries.

The activities of prolyl 4-hydroxylase and beta-glucuronidase, the concentration of hydroxyproline as well as reticulin and collagen type III, IV and V stainings were followed in skeletal muscle during a 20-day period after a 9-h treadmill running in untrained and trained male mice, aged 4-6 months. The prolonged 9-h running of untrained mice temporarily increased prolyl 4-hydroxylase activity 2, 5 and 10 days after exercise, more prominently in the red than in the white part of quadriceps femoris-muscle, and in analogical manner as beta-glucuronidase activity in tibialis anterior-muscle. Twenty days after exercise these enzymatic activities were back to the control level. The hydroxyproline content of red muscle was increased for 10 and that of white muscle for 20 days after the exertion. Training for 45 days did not affect hydroxyproline content and prolyl 4-hydroxylase activity was at the control level after the training. A 9-h exercise increased prolyl 4-hydroxylase activity much less in trained muscle than in the untrained muscle and did not affect muscle collagen content. Histological observations showed fiber necrosis 2 days and signs of fiber regeneration 5 days after the exertion in untrained mice. Twenty days afterwards the regeneration was nearly completed. Reticulin staining was increased in injured muscle areas 10-20 days after the exertion. In immunohistochemical staining, antibodies to all studied collagen types (type III, IV and V) showed increased staining 5-20 days after the exertion in the areas of muscle injuries and regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Morphological and enzymatic heterogeneity of suramin-induced lysosomal storage disease in some tissues of mice and rats.

Suramin-induced lysosomal storage disease reproduced in the rat was extended to the mouse with the attempt to characterize enzymatically and morphologically heterogeneous responses of various organs to the drug. Suramin administration strikingly decreased (3-6 days afterward) the activity of beta-glucuronidase in all tissues studied (kidney, liver, heart, and skeletal muscle). The enzymatic responses were small in the activities of beta-N-acetyl-glucosaminidase. The activity of arylsulfatase A decreased to a varying degree in mouse tissues, but in rats the activity increased in liver and skeletal muscle. The activity of cathepsin D increased in rat tissues. Suramin induced morphological changes characteristic to lysosomal storage diseases in kidney and liver but not in heart and skeletal muscle of both mice and rats. Kidney was appreciably more susceptible to suramin than liver. The occurrence of lysosomal accumulations, membranous lamellar inclusions, and granular material were most prominent in tubular cells of kidney and in Kupffer cells of liver. These cells also presented intensive Alcian blue staining. Interestingly, the enzymatic and morphological responses did not correlate with each other, which may reflect differences in the regulation of lysosomal functions in various cell types.

Acetylglucosaminidase↗

Bronchial changes in airborne tularemia.

We describe seven typhoidal tularemia patients without ulcers or lymphadenopathy, who underwent diagnostic bronchoscopy. Four patients had had obvious airborne exposure to F. tularensis during farming activities, and the remaining three had respiratory symptoms also. Bronchoscopical findings were pathological in all cases, varying from local to diffuse haemorrhagic inflammation; in one case a granulomatous tumour was seen. Early histopathological changes in three biopsies consisted of haemorrhagic oedema progressing to a non-specific inflammatory reaction, which could still be found 45 days after the onset of symptoms. Granulomatous inflammation, indistinguishable from tuberculosis or sarcoidosis, was seen in four biopsies from two patients, three to seven months after the onset. Most patients had radiographic hilar enlargement. We conclude that transmission of typhoid tularemia usually occurs through inhalation leading to bronchial changes, which correspond skin ulcerations in ulcero-glandular tularemia, the hilar enlargement corresponding to the lymph node component. We emphasize that usage of the term 'typhoidal' tularemia should be discontinued. Instead, tularemia transmitted through inhalation should be called pulmonary or respiratory.

Adult↗

Activities of some antioxidative and hexose monophosphate shunt enzymes of skeletal muscle in neuromuscular diseases.

The activities of some antioxidative and hexose monophosphate shunt enzymes, as well as of 2 hydrolases were studied in skeletal muscle biopsy specimens taken from 39 patients with neuromuscular diseases and from 15 controls. The activity of Se-dependent glutathione peroxidase was higher in patients with congenital myotonia, whereas in the other diagnostic groups this enzyme activity was the same as in the controls. The Se-independent and total glutathione peroxidase activity of patients in the various diagnostic groups did not differ from the controls. Moreover, no difference were observed in catalase activity between the patient groups and the controls. The activities of the rate limiting enzymes of hexose monophosphate shunt, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase of muscle biopsy samples of various patient groups did not show any significant difference from controls. The activity of a lysosomal hydrolase, beta-N-acetylglucosaminidase, was increased in patients with polyneuropathy and the activity of a nonlysosomal protease, alkaline protease, was high in patients with Charcot-Marie-Tooth disease. The activities of Se-dependent glutathione peroxidase, 6-phosphogluconate dehydrogenase and of both hydrolases showed a significant correlation to the magnitude of muscle atrophy.

Acetylglucosaminidase↗

Lysosomal changes in mouse skeletal muscle during the repair of exercise injuries.

Lysosomal changes of mouse skeletal muscle during the repair of exercise injuries were studied with biochemical, histochemical, and electron microscopic methods. Treadmill running for 4 hours and 9 hours increased the activities of cathepsin C and beta-glucuronidase, but not that of beta-glycerophosphatase in mouse quadriceps femoris muscle. The highest activities occurred 3 days after exertion and were higher after the longer duration of exertion. Similar changes that were highly correlated with the activities of lysosomal enzymes occurred in the activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase and in the concentration of DNA. The activities of lysosomal enzymes correlated significantly with the severity of histopathologic injuries. Histochemical stainings of beta-N-acetylglucosaminidase and beta-glucuronidase showed a strong increase in the staining intensity 3 and 5 days after exertion, both in inflammatory phagocytes and in surviving muscle fibers in the injured area, and staining intensities increased in parallel with the severity of injuries. Electron microscopy showed an increased number of autophagic vacuoles, lysosome-like bodies, and Golgi complexes in the fibers adjacent to necrotic foci, coinciding with the highest histochemical staining pattern. Lysosomal changes in surviving muscle fibers in close proximity to injured muscle fibers could, by autophagic degradation, provide structural elements for the regeneration of injured muscle fibers.

Animals↗

Latency differences of lysosomal enzymes in cardiac and skeletal muscles of male and female mice.

The purpose of this study was to compare the latencies of lysosomal enzymes (beta-glucuronidase, beta-N-acetylglucosaminidase, arylsulphatase and acid ribonuclease) in heart and in red and white skeletal muscle of male and female mice (Mus musculus). The unsedimentable, free activities together with releasable (Triton X-100, hypotonic shock and freeze-thawing treatments) and unreleasable, bound activities were assayed. The distribution of acid hydrolases to different fractions was strikingly heterogeneous. The most distinct differences occurred between the distributions of beta-glucuronidase and beta-N-acetylglucosaminidase. The differences between muscle types occurred in the activity levels of lysosomal enzymes, rather than in the fractional distributions. Sex-related differences were small and occurred mainly in the activity levels of heart muscle (higher in female mice). The results suggest that the heterogeneous distribution of lysosomal enzymes originates in the compartmental differences of lysosomal enzymes in muscle cells, rather than the differences in cell populations of different muscle types.

Acetylglucosaminidase↗

Phosphomannosyl receptors of lysosomal enzymes in cardiac and skeletal muscles of young and old mice.

The endogenous activity and the binding of high-uptake beta-N-acetylglucosaminidase were assayed in the membranes of heart and skeletal muscles of young (2 months) and old (15 months) NMRI-mice (Mus musculus) to evaluate the age-related changes in the phosphomannosyl receptors of lysosomal enzymes in muscular membranes. The total activities of beta-N-acetylglucosaminidase were significantly higher in cardiac and skeletal muscles of old than young mice. The total and the specific (inhibited by mannose-6-phosphate) binding of beta-N-acetylglucosaminidase to the membranes of cardiac muscle, but not to those of skeletal muscle, were higher in old mice than in young ones. The endogenous activity of beta-N-acetylglucosaminidase was significantly higher in the membranes of skeletal muscles of old mice than in those of young mice. The membranes of heart muscles did not show any difference in the endogenous activities. The saturation properties of the binding of beta-N-acetylglucosaminidase to the phosphomannosyl receptors were very similar in the membranes of heart and skeletal muscles of both age groups. We conclude that during aging the number of phosphomannosyl receptors of lysosomal enzymes increases in the membranes of heart muscle while the occupancy of phosphomannosyl receptors with endogenous ligands increases in the membranes of skeletal muscle.

Acetylglucosaminidase↗

Humoral immunity against Francisella tularensis after natural infection.

Forty-two subjects with acute tularemia were studied for the occurrence of C-reactive protein (CRP), and 73 subjects with acute tularemia or experience of the disease within the last 11 years were studied for immunoglobulin M (IgM), IgA, and IgG class-specific antibodies, agglutinating antibodies, and complement-fixing antibodies to Francisella tularensis by using an enzyme-linked immunosorbent assay (ELISA), the tube agglutination test, and a complement-fixing ELISA. The incubation time between infection and the outbreak of symptoms varied from 1 to 10 days, averaging 6.5 days. Elevated CRP concentrations were found in all samples taken in the first 6 days of illness, when the antibodies generally were absent. The highest CRP values, up to 165 mg/liter, occurred in the earliest samples and then decreased rapidly, being undetectable (less than 1 mg/liter) from 1 month after the onset of symptoms. Simultaneous though individually varying formation of IgM, IgA, and IgG class-specific antibodies to F. tularensis was demonstrable by ELISA in all the tularemia patients during the acute stage. In most cases, these antibodies appeared 6 to 10 days after the onset of symptoms, i.e., about 2 weeks after infection, reached their highest values at 4 to 7 weeks, and, despite a decreasing trend in their level, were still present 0.5 to 11 years after onset of tularemia, as demonstrable by the agglutination test and by the complement-fixing ELISA. Of the three methods used, ELISA for IgM, IgA, and IgG proved to be the most efficient for the early serodiagnosis of tularemia.

Adolescent↗

Airborne transmission of tularemia in farmers.

In a tularemia epidemic during 1982 in northern Finland, 53 patients showed no peripheral portal of entry for infection or associated lymphadenopathy. Respiratory symptoms were observed in 72% of the patients. 26/38 cases had abnormal chest films. Hilar adenopathy was the most common finding (36%). Four patients did not receive antibiotics; 43 received tetracyclines, 5 streptomycin and 1 cefuroxime and amoxycillin. All patients recovered. 50 patients acquired the infection during common farming activities, such as making fresh hay with a hay-cutter, handling dry hay, threshing, etc. Thus, airborne transmission may be an important source of infection in normal farming activities in endemic areas of tularemia.

Agriculture↗

Lysosomal changes in skeletal muscles during the repair of exercise injuries in muscle fibers.

Lysosomal changes were recorded in the skeletal muscles of mice and rats during the repair of muscle fiber injuries caused by a single bout of prolonged running. One purpose of the study was to characterize cellular and compartmental distributions of lysosomal enzymes and to investigate ultrastructural changes in the lysosomal system associated with the appearance and repair of muscle fiber injuries. Furthermore, the level of muscle fiber injuries was correlated with the lysosomal enzyme response and the indices obtained were utilized in the evaluation of the pathogenesis of exercise myopathy. The main results were: Heavy physical exertion caused scattered necrotic injuries of muscle fibers and inflammation in several skeletal muscles. The most susceptible muscles to exercise injuries were the red deep parts of quadriceps femoris muscle and the soleus and tibialis anterior muscles. The total activities of several lysosomal acid hydrolases, in particular those of beta/-glucuronidase, cathepsin C and arylsulphatase, strongly increased during the repair of exercise injuries. The highest responses occurred 3-5 days after exertion and the degree of enzyme responses correlated significantly with the level of histological injuries. The histochemical staining intensities of beta-N-acetylglucosaminidase and beta-glucuronidase were highest 3 and 5 days after exertion. An increased staining intensity occurred in the inflammatory phagocytes and in the surviving muscle fibers, especially in the red muscle fibers close to necrotic foci. An autophagic response occurred in the muscle fibers close to necrotic foci 2-7 days after exertion. Autophagic vacuoles were frequently small and contained different cellular structures at various stages of degradation. The number of lysosome-like bodies, Golgi complexes and multilamellar bodies also increased. Macrophages removed the debris of necrotic muscle fibers by heterophagic uptake 2-5 days after exertion. The unsedimentable and releasable activities of acid hydrolases increased more prominently than those of the total activities in homogenates and reached their highest values 3 days after exertion. The proportional distribution of various acid hydrolases to unsedimentable, releasable and bound fractions varied strikingly but remained appreciably stable throughout the exercise myopathy. The content of lysosomal phosphomannosyl-enzyme receptors in the membrane fraction was unchanged 0-3 days after exertion but a small increase occurred later. The endogenous receptor-bound activity of beta-N-acetylglucosaminidase was considerably increased 1-5 days after exertion but decreased later to the control level.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗