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Biomedical subjects

L Larsson

Publications and source records attributed to L Larsson.

At least 199 records · Page 11Linked to original sources

Experimental intestinal obstruction in rats. Studies on structure and disaccharidase activities.

An experimental model of congenital intestinal obstruction (CIO) was created in rats by means of fetal intrauterine surgery between the 16th and 20th days of gestation. By the use of a microsurgical technique areas at the mid-jejunum or the jejuno-ileal junction were infarcted by coagulation of mesenteric vessels. Gestation was terminated by Cesarean section within 24 hours before expected term to avoid cannibalism. The structure of the intestinal mucosal cells proximal and distal to the CIO at the light microscopy as well as the ultrastructure level was not changed indicating that the surgical method was successful. The activities of the brush border enzymes, maltase and lactase were significantly reduced distal to the obstruction as compared to controls. Proximal to the obstruction lactase was the only enzyme showing reduced activity in comparison to controls. These findings were not dependent on the localization of the obstruction or when it was performed and suggest that CIO causes selective changes of the biochemical properties of the cell membrane. The results are in agreement with the findings of disaccharidase activities in biopsies taken from human infants with CIO and point to the importance of a normal intestinal passage for the development of brush border enzymes.

Animals↗

Increased hip-fracture incidence in the county of Ostergötland, Sweden, 1940-1986, with forecasts up to the year 2000: an epidemiological study.

The incidence of hip fractures in the county of Ostergötland in Sweden has increased dramatically from 1940 to 1986, mainly due to an increase in age-specific incidence of trochanteric fractures. The increase is most pronounced in people over 80 but is present even in age groups down to 50 years. If the age-specific incidence rates continue to increase, and the population of the elderly grows in accordance with the forecast, there will be 70% more hip fractures in the year 2000 than in 1985.

Age Factors↗

Kinetic aspects of the removal of IgG and inhibitors in hemophiliacs using protein A immunoadsorption.

Seven patients with hemophilia A and B and 3 patients with acquired hemophilia were treated on 13 and 4 occasions, respectively, with protein A immunoadsorption to reduce anti-factor VIII or IX antibodies. Usually the patients were treated on 2 consecutive days. On each treatment day an average of 3 (range: 1.02-5.83) plasma volumes were processed in the congenital patients and 1.5 (range: 1.02-2.90) in those with acquired hemophilia. Plasma levels of IgG decreased from 18.9 +/- 1.9 to 3.1 +/- 1.2 g/l in the congenital group, and from 11.5 +/- 2.3 to 2.3 +/- 0.6 g/l in the acquired group. In the congenital hemophiliacs a corresponding reduction in inhibitor level of 70-95% was regularly seen; in 1 exceptional patient the inhibitor was reduced from 4,350 to 12 Bethesda Units/ml (BU/ml) during 5 days of treatment. In the congenital hemophiliacs immunoadsorption was followed by factor infusion to peak levels between 8 and 215 IU/dl. In the patients with acquired hemophilia a satisfactory reduction in inhibitor levels was obtained in 2 of the 4 treatments, which were followed by DDAVP or factor infusion. Some recommendations for the use of protein A immunoadsorption in the treatment of hemophilic patients will be given.

Adult↗

Spatial distribution of motor unit fibres in fast- and slow-twitch rat muscles with special reference to age.

The spatial arrangement and morphometrical properties of the muscle fibres within single motor units (motor unit fibres) were studied in fast-twitch units of the tibialis anterior (TA) and in slow-twitch units of the soleus, using a computer-assisted model. The motor unit fibres were identified by the glycogen-depletion technique and the position of each fibre was defined by (x, y)-coordinates. The distance between each fibre and the nearest motor unit fibre (nearest-neighbour distance), and the distance between each fibre and each of the other fibres in the unit (interfibre distance), was calculated and plotted. Comparisons were made between young adult (3-6 months) and old (20-25 months) rats. In old animals, the motor units of TA and the soleus were larger (P less than 0.05 and P less than 0.01), contained an increased number of muscle fibres (P less than 0.01) and covered a larger portion of the muscle cross-section (P less than 0.01 and P less than 0.1). These changes indicate the presence of an age-related denervation-reinnervation process in both types of muscles. In the young adult group, the fast-twitch motor unit fibres of TA were non-randomly arranged (P less than 0.05-0.01) whereas the fibre arrangement within the slow-twitch motor units of the soleus was not significantly different from random. In old animals, the fibre arrangement was non-random in both fast- and slow-twitch motor units. In TA, the distribution of nearest-neighbour distances showed an increased (P less than 0.05) proportion of short distances in old age, whereas the distribution of interfibre distances was unchanged. In the soleus, the distribution of interfibre distances showed an age-related displacement to the left at short distances (P less than 0.05) and to the right at long distances (P less than 0.01), but the distribution of nearest-neighbour distances was not significantly altered. It is concluded that motor unit fibres are non-randomly arranged in the fast-twitch motor units studied and that a non-random rearrangement of motor unit fibres takes place in both fast- and slow-twitch units during the ageing process. This age-related rearrangement is secondary to a denervation-reinnervation process and it appears as if different types of reinnervation predominate in fast- and slow-twitch units.

Aging↗

Effects of age on physiological, immunohistochemical and biochemical properties of fast-twitch single motor units in the rat.

1. Physiological, enzyme-histochemical, biochemical and morphometrical properties of fast-twitch single motor units were compared between young (3-6 months) and old rats (20-24 months) using the glycogen depletion technique. Monoclonal antibodies (mAbs) were used to identify the myosin heavy chain (MHC) composition in the muscle fibres of the motor unit (motor unit fibres) in order to facilitate correlative physiological, histochemical, biochemical and morphometrical studies. 2. Earlier observations on effects of age on contractile properties of fast-twitch motor units were confirmed and extended. That is, the duration of the isometric twitch, and the twitch and tetanus forces, were increased. Further, motor unit fibres were rearranged, occupying a larger territory and displaying an increased innervation ratio in old age, indicating a denervation-reinnervation process. 3. Motor units with muscle fibres expressing the novel IIX myosin heavy chain (MHC) were observed in both young and old animals, and they constituted the predominant motor unity type identified in the old animals. In contrast to the type IIX MHC motor units in the young animals, the type IIX MHC units in old age often contained muscle fibres which expressed either the type IIA or type IIB MHC, although type IIX MHC fibres were in the majority (so called 'IIX' MHC motor units), but motor units containing all these three fibre types were never observed. There were also single fibres co-expressing IIX and IIB MHCs in old age. 4. In the young animals the IIX MHC motor units had a higher (P less than 0.001) resistance to fatigue (fatigue ratio 0.45 +/- 0.11) than the type IIB MHC units (0.03 +/- 0.05), a succinate dehydrogenase (SDH) activity (0.62 +/- .007) intermediate (P less than 0.001) between those of type IIA muscle fibres classified according to myofibrillar ATPase activity after acid pre-incubation, i.e. type IIA ATPase, (0.84 +/- 0.13) and type IIB MHC motor unit fibres (0.20 +/- 0.04), and cross-sectional fibre areas (1650 +/- 320 microns 2) which were similar to those of type IIA ATPase muscle fibres (1460 +/- 150 microns 2) but smaller (P less than 0.001) than type IIB MHC motor unit fibres (4650 +/- 1180 microns 2).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphatases↗

MHC composition and enzyme-histochemical and physiological properties of a novel fast-twitch motor unit type.

Determinations of fatigue ratio, twitch and tetanus tension, and contraction and half-relaxation times of the isometric twitch were made in 21 single fast-twitch motor units from the rat tibialis anterior muscle. Single motor units were functionally isolated by microdissection of the ventral root, and the glycogen depletion technique was used to demonstrate the muscle fibers in the unit. Morphological and immuno- and enzyme-histochemical methods were applied to serial muscle cross sections to characterize the muscle fibers in the unit. Three of the units had muscle fibers of the IIa type according to staining both for myofibrillar adenosinetriphosphatase after acid preincubation and with the use of monoclonal antibodies specific for myosin heavy chains (MHCs), i.e., the IIa-MHC isoform. The other 18 units were of the IIb type according to enzyme-histochemistry, but immunohistochemistry showed that in six of these units the muscle fibers exhibited the novel type IIx-MHC isoform and in the other 12 units the IIb-MHC isoform. It was found that the IIx motor units have contraction and half-relaxation times similar to those of types IIa and IIb units but have morphological, physiological, and biochemical properties that distinguish them from the latter two types.

Animals↗

Characterization of murine thymic stromal-cell lines immortalized by temperature-sensitive simian virus 40 large T or adenovirus 5 E1a.

The heterogeneity of thymic stromal cells is probably related to their role in providing different microenvironments where T cells can develop. We have immortalized thymic stromal elements using recombinant retroviral constructs containing a temperature-sensitive simian virus 40 (SV40tsA58) large-T antigen gene or the adenovirus 5 E1a region linked to the gene coding for resistance to G418. Cell lines containing the thermolabile large T antigen encoded by SV40 proliferate at the permissive temperature of 33 degrees C and arrest growth when transferred to the nonpermissive temperature of 39 degrees C. At the nonpermissive temperature, ts-derived cell lines are shown to alter their phenotype but remain metabolically active, as indicated by the inducible expression of class I and class II MHC antigens. Here we describe the generation of a total of 84 thymic stromal-cell lines, many of which show distinct morphologic, phenotypic, and functional properties consistent with fibroblastoid, epithelial, or monocytoid origins. Several E1a and SV40tsA58-derived cell lines generated exhibit the epithelial characteristic of desmosome formation and, in addition, two of these lines (15.5 and 15.18) form multicellular complexes (rosettes) when incubated with unfractionated thymocytes from syngeneic mice. A single line (14.5) displays very strong nonspecific esterase activity, suggesting it may represent a macrophagelike cell type. We describe the generation of stromal cell lines with different properties, which is consistent with the heterogeneity found in the thymic microenvironment. In addition to documenting this diversity, these cell lines may be useful tools for studying T-cell development in vitro and give access to model systems in which stromal-thymocyte interactions can be examined.

Adenovirus Early Proteins↗

Bile increases lipopolysaccharide release in experimental E. coli peritonitis.

Previous studies in rats showed increased mortality when bile was added to intraperitoneally injected Escherichia coli. In the present study bacterial counts and levels of lipo-polysaccharide (LPS) were determined in the peritoneal cavity and in blood 0.5, 1, 4 and 10 hours after induction of peritonitis with E. coli alone or together with bile. LPS was measured with gas chromatographic analysis of beta-hydroxymyristic acid, a characteristic component of E. coli-LPS. Bacterial counts and LPS levels in peritoneal fluid and blood rose higher in E. coli + bile peritonitis than in E. coli peritonitis. The intergroup difference in LPS levels was evident at 0.5 and 1 hour, whereas the bacterial counts began to differ at 2 hours. Presence of intraperitoneal bile in E. coli peritonitis thus produced rapid rise in LPS levels that could not be caused by bacterial numbers alone. This early load of LPS may help to explain the noxious effect of bile in E. coli peritonitis.

Animals↗

The effect of excessive weight loss on skeletal muscle in man. A study of obese patients following gastroplasty.

Lean body mass, muscle biochemistry, enzymehistochemistry and muscle strength were analyzed before and after 10% and 18% body weight loss following gastroplasty in 16 obese patients. Subjective fatigue was also determined, using an arbitrary scale, before and after the operation. Lean body mass and alkali-soluble proteins (non-collagenic proteins) per DNA decreased significantly in the postoperative period. The proportions of type I and type II muscle fibers remained normal postoperatively. The muscle fiber area decreased significantly at 10% body weight loss, with a tendency towards restoration at 18% weight loss, despite continuing loss of lean body mass. Preoperatively the muscle strength, determined as maximum voluntary concentric and eccentric action of the knee extensor and flexor muscles, was not significantly different from that in sedentary, age-matched subjects, but was less than expected from the lean body mass, content of alkali-soluble proteins and muscle fiber size. Muscle strength was not significantly changed postoperatively. According to the fatigue scale, the patients' wellbeing was improved at 18% body weight loss compared with the preoperative status.

Adult↗

Expression of high molecular weight isoforms of CD45 by mouse thymic progenitor cells.

We have studied the expression of isoforms of CD45 (leukocyte common antigen, LCA) among T cell precursors using the organ culture system of Jenkinson et al. (Eur. J. Immunol. 1982. 12: 583). These experiments show that cells capable of recolonizing alymphoid embryonic thymic lobes in vitro can be detected in the thymus of fetal and adult mice and are enriched when thymocytes are depleted of cells bearing CD4 or CD8. These data are consistent with results from in vivo experiments of Fowlkes et al. (J. Exp. Med. 1985. 162: 802) indicating that T cell precursors lie within the double-negative (CD4-CD8-) compartment. No precursors were detected among the reciprocal populations of cells bearing CD4 and/or CD8 (single and double positives). Double-negative cell fractions were then divided on the basis of reactivity with monoclonal antibodies RA3-2C2 and RA3-3A1. These antibodies recognize the high molecular weight species of the LCA or, more accurately, a product defined by exon A of the CD45 gene. Recolonizing cells were found predominantly in the CD45RA+ (RA3-2C2 and RA3-3A1 reactive) fraction of double-negative thymocytes; CD45RA- enriched populations had increased efficiency of recolonization and CD45RA- depleted populations had decreased ability to recolonize as compared with the whole CD4-CD8- fraction. To clarify whether progenitors enriched in the CD45RA+ fraction were capable of giving rise to mature CD4+, CD8+ and CD4+ CD8+ cells, we analyzed the progeny of lobes seeded with CD4-CD8-CD45RA+ fractions. After 7-9 days in organ culture the proportion of CD4+, CD8+ or CD4+ CD8+ cells had increased to 35.2%, 18.6% and 23.7%, respectively (mean of five experiments), indicating that progenitors among the CD45RA+ population were indeed multipotent. These results suggest that the majority of T stem cells in the thymus are among thymocytes that express the CD45RA molecule, an hypothesis supported by our finding that removal of CD45RA-expressing cells (using complement and antibody) eliminated recolonizing capacity of thymic cell fractions.

Animals↗

Effects of different doses of alkaline citrate on urine composition and crystallization of calcium oxalate.

Prophylactic treatment with alkaline citrate in patients with recurrent calcium oxalate (CaOx) stone disease results in reduced CaOx supersaturation and increased urinary citrate. The effects of a single evening dose were compared with those of two and three daily doses in six recurrent CaOx stone formers with hypercalciuria, hypocitraturia or raised calcium/citrate quotients. While on a standardized hospital diet the patients were given 7.5 g (28 mmol) of sodium potassium citrate (URALYT-U) in one, two, and three doses. Fractional urine collections during 24 hours were analyzed for pH, composition, and crystallization risk (CR). All dosage regimens had favourable effects on urinary calcium, citrate, calcium/citrate quotients, and CaOx-CR. The most sustained effect was recorded with three divided doses. Single evening doses resulted in the most pronounced effects between 22.00-06.00 h, thereby counteracting the increased risk of CaOx crystallization during that period. In terms of 24h urine composition the best effect was recorded with alkaline citrate administered three times daily, but because of the favourable response by a single evening dose between 22.00-06.00 h the assumption was made that this dosage regimen might be sufficient to reduce the risk of CaOx crystallization and stone formation. However, the validity of such an assumption can only be established by long-term clinical studies.

Calcium Oxalate↗

Carcinoid granule extract contains antigenic determinants common to peptide hormone-producing cells and endocrine tumours.

Some soluble proteins, such as the chromogranins, are found in nearly all peptide hormone-producing cells. Little is known about their functional role, although they may act as enzymes or represent structural proteins. In the present study we have isolated granules from an ileal carcinoid tumour and raised antibodies to protein constituents within them. The antiserum proved to be useful for the immunohistochemical demonstration of peptide hormone-producing endocrine tumours in general and for the demonstration of most peptide hormone-producing cells.

Animals↗