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Biomedical subjects

S Eriksson

Publications and source records attributed to S Eriksson.

At least 415 records · Page 23Linked to original sources

Effects of smoking and intermediate alpha 1-antitrypsin deficiency (PiMZ) on lung function.

To assess the role of smoking and heterozygous (PiMZ) alpha 1-antitrypsin deficiency as risk factors in the pathogenesis of emphysema, we compared results of FEV1.0 (and FEV%) measurements in a random population sample of 56-year-old men with those obtained in an investigation 6 years earlier. We studied 32 PiMZ heterozygotes (14 smokers) and 31 PiM controls (13 smokers), representing 81% of the initial series. The annual decline in FEV1.0 values in non-smoking 56-year-old PiMZ men did not differ from PiM controls (smokers or non-smokers). In contrast, smoking heterozygotes showed a significantly higher mean annual decrease in FEV1.0 than non-smoking heterozygotes (75 ml and 40 ml/year respectively). In spite of this evidence of a modest accelerating effect on lung ageing among smoking PiMZ subjects during the 6 years covered by the study, no increased prevalence of clinical obstructive lung disease was noted.

Forced Expiratory Volume↗

Studies in vitro on the uptake and degradation of sodium hyaluronate in rat liver endothelial cells.

Rat liver endothelial cells in primary cultures at 7 degrees C bind radioactively labelled sodium hyaluronate (HA; Mr 400 000) specifically and with high affinity (Kd = 6 X 10(-11) M). Maximal binding capacity is approx. 10(4) molecules per cell. Inhibition experiments with unlabelled HA and oligosaccharides from HA indicate that each molecule is bound by several receptors acting co-operatively and that the single receptor recognizes a tetra- or hexa-saccharide sequence of the polysaccharide. At 37 degrees C the liver endothelial cells endocytose the HA. The process combines the features of a receptor-mediated and a fluid-phase endocytosis. The rate of internalization does not show any saturation with increasing HA concentration, but is approximately proportional to the polysaccharide concentration at and above the physiological concentration. At 50 micrograms of free HA/l each liver endothelial cell accumulates 0.1 fg of the polysaccharide/min. Fluorescent HA accumulates in perinuclear granules, presumably lysosomes. Degradation products from HA appear in the medium about 30 min after addition of the polysaccharide to the cultures. The radioactivity from HA containing N-[3H]acetyl groups or 14C in the sugar rings is recovered mainly as [3H]acetate and [14C]acetate respectively. Estimations of the capacity of liver endothelial cells to internalize and degrade HA in vitro indicate that these cells may be primarily responsible for the clearance of HA from human blood in vivo.

Animals↗

Cell cycle-dependent regulation of mammalian ribonucleotide reductase. The S phase-correlated increase in subunit M2 is regulated by de novo protein synthesis.

Ribonucleotide reductase in mammalian cells is composed of two nonidentical subunits, proteins M1 and M2. Protein M2 contains a tyrosyl free radical, essential for activity, which can be quantified directly in frozen, packed cells by EPR spectroscopy. A 3-7-fold increase in the concentration of tyrosyl radical-containing M2 subunit was observed when mouse mammary tumor TA 3 cells passed from the G1 to the S phase of the cell cycle. Similar results were obtained with cells synchronized by isoleucine starvation or separated by centrifugal elutriation. Addition of deuterated tyrosine to cells give rise to a different EPR signal in newly synthesized protein M2. Pulse-chase experiments with deuterated tyrosine showed unequivocally that the S phase-correlated increase in radical-containing M2 subunit was due to de novo protein synthesis. Labeled M2 molecules disappeared with a half-life of 3 h, and therefore new molecules must be synthesized at a high rate during the S phase. In contrast, after hydroxyurea inactivation, cells rapidly regenerated the tyrosyl radical in already existing protein M2 molecules. This enzyme activation mechanism is clearly different from the one responsible for regulating protein M2 activity during the cell cycle.

Animals↗

Alpha 1-antitrypsin deficiency: some personal experiences.

A short review is given on the discovery of the alpha 1-antitrypsin deficiency, a hereditary metabolic defect, in 1963, its biochemical identification, the recognition of its typical clinical manifestations and effects on lung physiology. Several genetic variants are mentioned. The gradual development of the concept of proteolytic digestion of lung elastin by excess of leucocyte elastase as a basic phenomenon in the pathogenesis of emphysema is discussed in some detail.

History, 20th Century↗

Central and peripheral haemodynamic effects of non-steroidal anti-inflammatory drugs in man.

The haemodynamic effects of non-steroidal anti-inflammatory (NSAI) drugs can be attributed either to their common property of inhibiting the formation of prostaglandins (PG) in the cardiovascular system, or to direct actions on the tone and sensitivity of the resistance vessels in various regions. Indomethacin (IND) is the most frequently studied NSAI drug, in animals and in man. Its cardiovascular effects differ somewhat from those of other NSAI, due to the fact that, besides inhibiting PG formation, IND acts as a direct vasoconstrictor. The stimulatory effect of IND in vascular smooth muscle results in an increased systemic vascular resistance which, although partially compensated by a decreased cardiac output, gives rise to a moderate increase in systemic blood pressure. The vasoconstrictor effect of IND is of particular interest in patients with ischemic heart disease, since it lowers their already decreased coronary flow, and may thereby accentuate the risk of myocardial infarction. Administration of IND also leads to a decreased blood flow in the splanchnic region, the kidneys, and the brain. The cerebral blood flow is lowered by 25-35%; in addition, IND almost entirely erases the hyperemic flow response to hypercapnia. Of other NSAI drugs, at least aspirin and naproxen are completely devoid of such actions on the cerebral circulation. A common vascular effect of all NSAI drugs is a diminution of reactive hyperemia, the local hyperemia that develops in a tissue subjected to a short period of arterial occlusion. Part of this hyperemic response is dependent on an intact vascular PG formation and consequently it is inhibited when PG formation is blocked. In contrast, NSAI drugs do not affect the functional increase in the blood flow in working skeletal muscle.

Adult↗

Deoxyribonucleoside triphosphate metabolism and the mammalian cell cycle. Effects of thymidine on wild-type and dCMP deaminase-deficient mouse S49 T-lymphoma cells.

The size of the dCTP pool has been implicated as a possible regulator of DNA synthesis. In this investigation we correlate large intracellular variations in deoxyribonucleoside triphosphate levels to the growth rates and cell-cycle kinetics of mouse S49 T-lymphoma cells. Wild-type and a mutant line AzidoC-100-5, lacking dCMP-deaminase activity resulting in a 10-fold expanded dCTP pool were studied and compared using flow cytometry, centrifugal elutriation and nucleoside triphosphate determinations. An increase in the dCTP pool was closely correlated to the passage of cells from G1 to S phase in both cell types. Addition of thymidine to wild-type and mutant cells resulted in an accumulation of cells in early S phase, concomitant with a decreased dCTP level. Mutant cells excreted large amounts of deoxycytidine into the medium which partially protected the cells from thymidine inhibition. The doubling times for the mutant and wild-type cells were very similar but the mutant had a somewhat prolonged S phase and shortened G1 phase compared with the wild-type cells. Large changes in the DNA precursor levels were produced by addition of thymidine to mutant cultures. This gave no change in the growth rate but a somewhat shortened S phase and prolonged G1. The biochemical background for these effects is discussed.

Animals↗

Aetiological aspects on primary liver cancer with special regard to alcohol, organic solvents and acute intermittent porphyria--an epidemiological investigation.

Some environmental factors of possible aetiological importance for primary liver carcinoma (PLC) in males were analysed in a case-control study including 83 cases of hepatocellular carcinoma (HCC), 15 cases of intrahepatic cholangiocellular carcinoma (CC), 3 cases of haemangiosarcoma and 1 case of unspecified sarcoma in the liver--102 cases in total. Two matched controls were used in each case. One case with haemangiosarcoma was exposed to polyvinyl chloride. The case with unspecified soft-tissue sarcoma was exposed to phenoxy acids. A 4-fold increase in the risk of HCC was seen in alcoholics, and regular drinking gave a 3-fold increase in the risk. Exposure to organic solvents gave a 2-fold increase in the risk of HCC. No increased risk was observed for cases exposed to various other chemicals. Three cases of HCC had a previous diagnosis of porphyria acuta intermittens (PAI), versus no control. Six cases of HCC had a previous diagnosis of porphyria acuta intermittens (PAI), versus no control. Six cases with PLC had polyphyria cutanea tarda (PCT) which in 4 cases was related to alcoholism and in one case to haemochromatosis.

Acute Disease↗

Monoclonal antibody specific for the mutant PiZ alpha 1-antitrypsin and its application in an ELISA procedure for identification of PiZ gene carriers.

The PiZ genetic variant of alpha 1-antitrypsin in its homozygous form is associated with an increased risk for chronic lung and liver disease. About 5% of the population are carriers of one PiZ deficiency gene resulting in intermediate levels of plasma alpha 1-antitrypsin (PiMZ, PiSZ, PiPZ). We report the preparation of a hybridoma cell line, ATZ 11, produced by fusion of spleen cells from BALB/c mice immunized with a purified liver PiZ alpha 1-antitrypsin and Sp 2/0 Ag 14 mouse myeloma cells. ATZ 11 produces monoclonal antibodies (IgG1 kappa) specifically interacting with PiZ alpha 1-antitrypsin. These antibodies were used in an ELISA procedure permitting easy and accurate identification of PiZ gene carriers. The method is especially well-suited for studying large population samples concerning the putative relationship between intermediate alpha 1-antitrypsin deficiency and disease.

Animals↗

Comparative investigation of the antiarrhythmic effect of propafenone (Rytmonorm) and lidocaine in patients with ventricular arrhythmias during acute myocardial infarction.

Propafenone, a new class I antiarrhythmic drug, given as a bolus injection followed by oral medication, or lidocaine were given to 20 consecutive patients admitted with chest pain suggesting acute myocardial infarction and showing high grades, i.e. multiform, pairs or R-on-T premature ventricular complexes or short runs of ventricular tachycardia. Before institution of therapy the mean number (+/- 1 SD) of premature ventricular contractions (PVCs) per hour was 169 +/- 123 in the lidocaine group and 324 +/- 440 in the propafenone group. During the next 24 hours lidocaine reduced the numbers of PVCs by 73% and propafenone by 75%. The mean number (+/- 1 SD) of 5-minute periods with high grade PVCs was 4.3 +/- 2.9 in the lidocaine group and 5.8 +/- 4.5 in the propafenone group. During therapy this number was equally reduced in both groups to 2.4. One patient in the lidocaine group developed ventricular fibrillation and three patients in the propafenone group were excluded because of increasing numbers of PVCs. One patient in the propafenone group showed a torsade-de-pointes ventricular tachycardia.

Aged↗

Pulmonary-artery cineangiocardiography to demonstrate cardiac thrombi in patients with cerebral infarction.

The usefulness of pulmonary-artery cineangiocardiography (PACAC) to demonstrate intracardiac thrombi in patients with cerebral infarctions of possible embolic origin has been explored. PACAC was performed in 60 patients (mean age 74 years) with sudden onset of permanent neurological deficits in whom CT scan and CSF analyses had excluded intracerebral hemorrhage. Opacification of the left atrium was excellent in 52 (87%) investigations, acceptable in 7 and poor in 1. Among 33 patients with chronic atrial fibrillation, an atrial thrombus was demonstrated in 8 (24%) and a suspected thrombus in 3. Atrial clot was also demonstrated in a patient with intermittent atrial fibrillation. In 4 out of 14 patients with previous myocardial infarction, a ventricular thrombus was demonstrated. Ventricular clots were detected in 2 of 46 patients without known previous myocardial infarction. No major complications occurred during the investigation. PACAC can be to used in the search for atrial or ventricular thrombi when cardiac source of a cerebral embolus is suspected. About 1 out of 3 patients with atrial fibrillation has remaining intracardiac thrombus after stroke.

Aged↗

Vasopressin release in response to acute hypotension induced at different time intervals in the conscious sheep.

The renal arginine vasopressin (AVP) excretion in response to acute systemic hypotension induced by intravenous infusion of sodium nitroprusside (SNP) (30-40 micrograms/kg min-1) at different experiment intervals (0, 2, 4, 7 and greater than or equal to 12 days) was studied in the conscious hyperhydrated sheep. During the first post-infusion hour, 2.5 times more AVP was excreted in response to hypotension induced at greater than or equal to 12 day intervals than that observed at intervals of 0-7 days. No interexperimental time dependence of the AVP response to SNP infusion was seen with intervals of 0-7 days. The attenuated AVP release obtained with reduced experiment intervals (0-7 days) was accompanied by shorter antidiuresis and a less accentuated natriuresis during the post-hypotensive period in comparison to what was observed with greater than or equal to 12 day experiment intervals. There were no interval-dependent differences in maximal fall of mean arterial pressure, or onset and recovery of the hypotension induced by SNP administration. It is suggested that acute systemic hypotension causes such a massive AVP release that more than one week is needed for complete restoration of a releasable neurohypophyseal pool of the hormone.

Animals↗

The urine smell around patients with urinary incontinence. The production of ammonia in ordinary diapers and in diapers impregnated with copper acetate.

The foul smell of urine around patients with urine incontinence is thought to be due mainly to the production of ammonia from urea by bacterial ureases. The production of ammonia was thus measured by infrared spectrophotometry in control diapers and in test diapers impregnated with copper acetate (CA), after use by urine-incontinent patients with persistent bacteriuria. The CA-impregnated diapers produced significantly less ammonia than the control diapers. The CA-impregnated diapers were not bactericidal, however. The results are consistent with the hypothesis that the smell reduction of the CA-impregnated diapers is due to a bacteriostatic action or an inhibition of bacterial ureases by CA.

Aged↗

Evidence of increased intestinal synthesis and extracellular deposition of IgM in primary biliary cirrhosis. An immunofluorescence study of liver and small-intestinal biopsy specimens.

Direct immunofluorescence showed intense extracellular granular deposition of IgM and C3 in liver and small-intestinal biopsy specimens from patients with primary biliary cirrhosis. In contrast, IgM deposits were not observed in liver tissue from patients with other liver diseases, whereas small-intestinal IgM deposits were seen also in 2 of 17 patients with various intestinal disorders. The tissue deposition of IgM did not vary with plasma IgM levels, degree of cholestasis, or histological stage of the disease but seemed to reflect an abnormal property of the IgM molecule. The number of IgM-positive mononuclear cells in intestinal mucosa from patients with primary biliary cirrhosis was markedly increased, suggesting increased local synthesis of IgM. Deposition of IgM with complement-activating ability might contribute to the development of tissue damage in primary biliary cirrhosis. In addition, the apparent specificity of these IgM deposits in liver for primary biliary cirrhosis might be of diagnostic value when histological classification is difficult.

Aged↗

The prevalence and clinical spectrum of primary biliary cirrhosis in a defined population.

We studied 33 patients with primary biliary cirrhosis representative of a well-defined population (240,000) during the decade 1973-82. Mean annual incidence was 13.7 per 10(6) and point prevalence, 92 per 10(6) inhabitants in 1982. An accumulation of asymptomatic cases, constituting 45% of all patients, with a normal life expectancy accounted for this high prevalence. During the study period no disease progress was seen in asymptomatic patients, in contrast to a 50% mortality in the symptomatic group. Disease progress in the latter group was reflected by deterioration of N-demethylating capacity and increasing bilirubin levels. Although our data confirm an increasing prevalence of primary biliary cirrhosis, the mortality rate during the study period was almost identical to that in an earlier period, 1951-60.

Female↗