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Biomedical subjects

L Carlsson

Publications and source records attributed to L Carlsson.

At least 163 records · Page 9Linked to original sources

Mechanisms of local noradrenaline release in acute myocardial ischemia.

The present study was performed in order to examine some of the characteristics of the local impulse-independent release of noradrenaline (NA) seen in acute myocardial ischemia. Experiments were carried out mainly in isolated perfused rat hearts submitted to either global coronary flow reduction or ligation of the left coronary artery. An increased efflux of NA, with a concomitant reduction in the tissue content of NA, was observed during reperfusion after only 7.5 min of coronary artery occlusion. Under conditions of global flow reduction, increased amounts of NA appeared in the venous effluent after 10-15 min of ischemia. The NA efflux progressively increased with the duration of ischemia. The maximal efflux of NA was observed during the first min of reperfusion, after which the efflux declined rapidly. Partial reduction or omission of calcium from the perfusion medium, anoxic reperfusion or presence of verapamil did not attenuate the efflux of NA and its metabolites during ischemia and/or reperfusion. Presence of desipramine, an inhibitor of the carrier-mediated transport of catecholamines, markedly reduced the ischemia-induced release of NA and simultaneously attenuated the efflux of NA metabolites. Maintenance of anaerobic glycolysis was of crucial importance for the retention of NA during ischemia. No sign of enhanced NA efflux was observed during ischemia in hearts perfused with exogenous glucose, or in hearts in which the oxidative phosphorylation was inhibited. Induction of ischemia in hearts perfused with lactate, pyruvate or acetate as exogenous substrate, in hearts in which the glycolytic pathway was inhibited, or in hearts depleted from their glycogen stores was associated with an increased efflux of NA. Depletion of myocardial NA stores with alpha-methyl-meta-tyrosine (alpha-MmT) caused a significant reduction in both the incidence of ventricular fibrillation and the mortality rate after left coronary artery ligation in anesthetized rats. The alpha-MmT pretreatment did not reduce arterial blood pressure, heart rate, myocardial energy charge or glycogen levels. It is concluded that acute myocardial ischemia is associated with an increased local release of NA, and that this release may play an important role in the genesis of early ischemic arrhythmias. An important part of the ischemia-induced release of NA is, in all probability, mediated by a carrier-mediated transport mechanism, and inhibition of this mechanism may be a specific approach to attenuate the NA release and thus minimizing its detrimental consequences.

Acute Disease↗

Osseointegration of titanium implants.

Forty-eight screws, six double cylindrical implants and six T-plates were inserted into the tibia or femur of 6 dogs. Two titanium screws were inserted into the proximal tibia of 5 patients to anchor a titanium mould. The implants were removed en bloc with adjacent bone tissue after 3 to 14 months. They were sectioned using a technique that allowed analysis of the intact tissue-to-metal specimens. Osseointegration, defined as a direct bone-to-implant contact without interposed soft tissue, was confirmed in all screw-shaped implants while the cylindres had only partial bone contact as did the T-plates. We conclude that osseointegrated implants may be applicable in joint reconstruction for arthrosis or rheumatoid arthritis.

Adult↗

Objective quantification of tremor in conscious unrestrained rats, exemplified with 5-hydroxytryptamine-mediated tremor.

To accomplish an objective quantification of tremor in conscious unrestrained rats, a registration device based on accelerometry was developed. Tremor intensity was continuously recorded by a small piezoresistive accelerometer (Egal 125-10D, Entran Devices) mounted on the back of the freely moving rat. The accelerometer was connected to a Grass Polygraph, where the analog signal was quantified as arbitrary marks/min by a 7P10 integrating unit. The integrated signals were then further analyzed by a desk-top computer (Luxor ABC-80). By analyzing tremor response to central serotonergic system activation, the reproductibility as well as the advantages and limitations of this recording system were demonstrated.

5-Hydroxytryptophan↗

Antigenic determinants of pregnancy-associated alpha 2-glycoprotein and alpha 2-macroglobulin defined by poly- and monoclonal antibodies.

Human alpha 2-macroglobulin and pregnancy-associated alpha 2-glycoprotein (PA alpha 2G) share several physicochemical characteristics. By the use of unabsorbed or absorbed polyclonal antibodies to these antigens, the existence of common epitopes in these molecules were demonstrated in crossed immunoelectrophoresis. Two monoclonal antibodies out of 9 raised against purified PA alpha 2G were demonstrated to react with both antigens, indicating close immunochemical relatedness between these macroglobulins. The findings might have functional implications.

Animals↗

Ischemia-induced local release of myocardial noradrenaline.

The isolated perfused rat heart, prelabelled with 3H-noradrenaline (NA), was used to examine the ischemia-induced release of myocardial NA, and to investigate to what extent reperfusion of an ischemic myocardium per se causes a release of NA. In a model of global myocardial ischemia with 90% flow reduction and the use of lactate as perfusion substrate, release of 3H-NA into the perfusate was already observed during the first 10-20 min of ischemia. The quantities of 3H-NA released increased further with increasing duration of ischemia. In another model with regional ischemia produced by left coronary artery ligation, a similar, though less marked, release of 3H-NA into the perfusate was observed during ischemia. Reperfusion after 60 min of ischemia was associated with a marked outflow of 3H-NA and 3H-NA metabolites, which was not reduced if reperfusion was performed with a Ca2+-free buffer. Furthermore, in the globally ischemic heart model, the relative amounts of 3H-NA and the various 3H-NA metabolites in the effluent remained constant during the last minute of ischemia and the first minute of reperfusion. We concluded that ischemia is associated with early local release of myocardial NA. NA can partly be trapped in the ischemic tissue and washed out during reperfusion.

Adenosine Triphosphate↗

Antiarrhythmic effect of reducing myocardial noradrenaline stores with alpha-methyl-meta-tyrosine.

In the adrenergic neurons the amino acid alpha-methyl-meta-tyrosine (alpha-MmT) is converted to metaraminol via the noradrenaline (NA) synthetic pathway. Metaraminol thereby displaces NA from its neuronal stores, and as a consequence NA levels can be drastically reduced, although normal sympathetic tone is essentially maintained by release of newly synthetized NA. In rats treated with alpha-MmT methylester (400 + 200 mg/kg) myocardial NA was reduced to less than 10% of control. Under barbiturate anesthesia, the left coronary artery was ligated, and the incidence of ventricular fibrillation and mortality during a 30-min period was recorded. Before ligation, mean arterial blood pressure was unchanged and heart rate slightly increased by alpha-MmT pretreatment. The energy state of the myocardium was also unchanged by the alpha-MmT pretreatment, as seen in a separate study where hearts from identically treated rats were taken for analysis of glycogen and adenine nucleotides. Thus, alpha-MmT pretreatment appeared not to have reduced the sympathetic tone of the heart. In spite of this, alpha-MmT pretreatment reduced the ventricular fibrillation from 65 to 33% (p less than 0.01; chi 2 test) and mortality from 37 to 15% (p less than 0.05). The results indicate an important role of myocardial NA stores in the development of early ischemic arrhythmias.

Animals↗

Gas exchange during mechanical ventilation.

In an experimental model using a Servo-ventilator (Siemens-Elema, Sweden) oxygen consumption (V'O2) and carbon dioxide production (V'CO2) were measured at varying FIO2. Gas exchange was simulated by adding N2 or CO2 to the inspiratory line of the ventilator. Inspiratory and expiratory gases were collected in Douglas bags for analyses by a mass spectrometer. The residual standard deviation for the regression of measured V'O2 on predicted V'O2 was 14 ml/min and did not significantly differ from the line of identity. For V'CO2 the corresponding residual standard deviation was 3 ml/min. This regression line deviated by -3% from the line of identity.

Carbon Dioxide↗

Growth hormone (GH)-releasing factor (GRF) pretreatment enhances the GRF-induced GH secretion in rats with the pituitary autotransplanted to the kidney capsule.

The long term in vivo effects of the recently characterized human pancreas GH-releasing factor, hpGRF (1-44) were studied in chronically cannulated unrestrained rats. In order to minimize the influence of endogenous hypothalamic GRF and somatostatin on the pituitary, the experiments were carried out in rats with the pituitary autotransplanted to the kidney capsule. The integrated GH release (mean +/- SE) in response to an iv injection of hpGRF (4 micrograms/kg) was markedly enhanced (P less than 0.01) by iv pretreatment with hpGRF every 8 h for 3 days (182 +/- 47 h X ng/ml) as compared to saline-pretreated controls (36 +/- 4 h X ng/ml). TRH pretreatment did not potentiate the effect of hpGRF (47 +/- 9 h X ng/ml). It is concluded that multiple administrations of hpGRF enhance the GH response to a subsequent hpGRF injection in the rat. Moreover, autotransplantation of the pituitary to the kidney capsule may supply a useful in vivo model for further studies on the effects of different modes of GRF administration on GH secretion.

Animals↗

Glare from outdoor high mast lighting: effects on visual acuity and contrast sensitivity in comparative studies of different floodlighting systems.

Glare effects on visual acuity and contrast sensitivity were studied at outdoor timber terminal work with conventional far-reaching floodlighting and with a new type of oblique floodlighting with an asymmetrical light distribution. The binocular work visual acuity of 19 volunteers was measured at 40, 55 and 80 per cent contrast and the contrast sensitivity of 14 volunteers at spatial frequencies of 0.5, 1, 2, 4, 8 and 16 cycles/degree. With the light source 15 degrees from the centre of the visual fields the visual acuity as well as the contrast sensitivity was consistently lower with the conventional type than the new type of floodlight . The results thus indicate that not only the vision of details is impaired by glare but also the contrast perception of sparse patterns. In standardized rating scales the timber terminal workers scored the difference in glare between the two floodlight systems as "great"--"very great".

Adult↗

Exposure to and effects of glare from high mast lighting on workers at a timber terminal.

High mast floodlighting at outdoor workplaces has economic advantages but suffers from shortcomings such as glare. This study was made to collect and evaluate data from a situation with glare from a physical and occupational health standpoint. When unloading timber, the worker's gaze is frequently directed upward, whereas conventional glare indexes for luminaires assume the gaze is diagonally downwards. It was found that reduced visual acuity could cause difficulty in normal working routines.

Journal Article↗

Ischemia-induced noradrenaline release in the isolated rat heart: influence of perfusion substrate and duration of ischemia.

To examine some of the characteristics of the local noradrenaline (NA) release in myocardial ischemia a study was made on Langendorff-perfused rat hearts, prelabelled with 3H-NA. The left coronary artery was ligated for 15, 30, 60 or 120 min, followed by 10 min of reperfusion. The coronary effluent was collected and analyzed for radioactivity to indicate release of 3H-NA. In some of the experiments the fraction of 3H-NA was determined. As substrate in the perfusion medium either glucose (11.1 mM) or sodium lactate (5.0 mM) was used. During the ischemic period there was a slight decrease in the outflow of radioactivity. However, reperfusion was associated with a rapid and marked outflow of radioactivity, including an increased fraction of 3H-NA, in the effluent. Compared to glucose as perfusion substrate, lactate caused a significantly higher (P less than 0.01) outflow of tritiated substances after 60 and 120 min of regional ischemia. With lactate there was an almost linear relationship between reperfusion efflux of 3H and duration of ischemia. With glucose, the reperfusion outflow increased less rapidly after a duration of ischemia longer than 15 min. It is concluded that the degree of local NA release in myocardial ischemia depends on both the duration of the ischemic period and the substrate used. Glucose attenuates the reperfusion outflow of NA, especially after longer periods of ischemia. The effect may be due to decreased myocardial cell damage with this substrate and/or a direct protection of the adrenergic nerve endings.

Animals↗

A monoclonal antibody-enzyme immunoassay for serum carcinoembryonic antigen with increased specificity for carcinomas.

A two-site monoclonal antibody-enzyme immunoassay (MEIA) for carcinoembryonic antigen (CEA) was developed that uses two monoclonal anti-CEA antibodies, which recognize two different epitopes in the peptide moiety of CEA. The assay was sensitive to 0.5 micrograms/liter and had a measuring range of 0.5-200 micrograms of CEA per liter. It was highly specific inasmuch as none of three known CEA-related substances, "nonspecific crossreacting antigens 1 and 2" (NCA-1 and NCA-2) and biliary glycoprotein I (BGP I), reacted in the assay. NCA-2 (meconium antigen) is very similar to CEA. None of five commercially available CEA assays were able to differentiate between CEA and NCA-2. With one exception (colon), normal tissue extracts did not react in the MEIA even when tested at very high concentrations. Sera from a total of 180 healthy individuals and patients with malignant and nonmalignant disease were analyzed for CEA levels by using the MEIA and in parallel a conventional radioimmunoassay. A significant increase in specificity for carcinomas was obtained with the MEIA. This was essentially due to a decrease of MEIA CEA values in sera from patients with nonmalignant disease. The CEA values in the group of carcinoma patients (colon, pancreas, lung, and breast) were the same in the two assays.

Antibodies, Monoclonal↗

ADP-ribosylation of the Mr 83,000 stress-inducible and glucose-regulated protein in avian and mammalian cells: modulation by heat shock and glucose starvation.

ADP-ribosylation of proteins was analyzed by in vivo labeling of cells with [3H]adenosine, followed by separation of their protein components by two-dimensional isoelectric focusing/NaDodSO4 polyacrylamide gel electrophoresis. We show here that in several cell types of avian and mammalian origin the major [34H]adenosine acceptor in vivo is a polypeptide with a Mr of 83,000 and isoelectric point of approximately equal to 5.3. This polypeptide is identical to one of the stress-inducible and glucose-regulated proteins (here called SP83) previously described in avian and mammalian cells. Snake venom phosphodiesterase digestion of purified 3H-labeled SP83 releases 5'-AMP and a minor fraction of 2'-(5"-phosphoribosyl)-5-AMP. In vitro labeling with [32P]NAD+ of total cell lysates made in the presence of non-ionic detergents also results in incorporation of radioactivity into SP83. Both of these results strongly suggest that the modification is an ADP-ribosylation. Heat shock and glucose starvation of cells induce a rapid and extensive decrease in the incorporation of ADP-ribose into SP83, suggesting that ADP-ribosylation may be important for the regulation of the function of this protein.

Adenosine↗

Effect of metabolic control and duration on exercise-induced albuminuria in diabetic teen-agers.

Nineteen type I diabetic teen-agers without clinical signs of nephropathy with a duration of diabetes varying from 3 to 16.8 years were examined by a standardized exercise test for analysis of urinary excretion of albumin and beta 2-microglobulin. The patients were studied both in poor and improved (but not perfect), metabolic control as defined by HbA1c and blood glucose profiles, and the values were compared to those of 14 age-matched healthy controls. The controls showed no increase in albumin excretion rate during exercise as was found in diabetic patients. The albumin excretion rate during exercise was significantly correlated (p less than 0.05) to systolic blood pressure in the diabetic patients. Blood pressure in the diabetic patients was, however, similar to that of controls both at rest and during exercise. Urinary beta 2-microglobulin did not change during exercise. The urinary albumin excretion during exercise decreased significantly with improved metabolic control in diabetic patients, but the albumin excretion rate was not correlated with either blood or urinary glucose or diuresis during the exercise test. When metabolic control was improved there was a significant correlation between the increase in albumin excretion rate during exercise and the duration of diabetes, indicating that part of the exercise-induced albumin excretion might reflect irreversible morphological changes in the diabetic kidney. This test might therefore have a predictive value for diabetic nephropathy if performed during strict metabolic control.

Adolescent↗

On the dynamics of the microfilament system in HeLa cells.

We measured the pools of unpolymerized and filamentous actin in homogenates of HeLa cells made in several different lysis buffers, as well as after treatment of cells with a variety of chemicals or trypsin, and after adenovirus (type 2) infection. This was possible when a series of factors concerning the basic culture conditions were kept constant: e.g., serum type used, serum batch, cell density, time after subcultivation of cells, and buffering substance in the medium. Homogenates from untreated cells usually contain 35-45 percent of the total actin in an unpolymerized form. With some batches of cells this number can be as high as 50 percent. In sparse cultures (3 x 10(4) cell/cm(2)), HeLa cells contain approximately 10 pg actin/cell, while the corresponding number is only 5 pg in dense cultures (3 x 10(5) cells/cm(2)). Treatment of cells with cytochalasin B increases the pool of unpolymerized actin by approximately 30-40 percent, while colchicine decreases the fraction of unpolymerized actin by 20 percent. The oxidant diamide increases the filamentous actin pool 25-50 percent. Glucose, sodium azide, dinitrophenol, serum starvation, or thymidine treatment does not affect the distribution between unpolymerized and filamentous actin to any significant extent. Trypsin and EDTA induced rounding up of cells but did not change the actin distribution. The distribution of actin between G- and F-forms was unchanged after adenovirus infection. These results show that significant changes in the actin pools can be induced in nucleated cells. However, several treatments which alter the morphology and motility of cells are not accompanied by an alteration in the G-/F-actin ratio.

Actins↗