FISH mapping of the porcine vWF gene to chromosome 5q21 extends synteny homology with human chromosome 12.
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Animals↗
Biomedical subjects
A Sjöberg
Publications and source records attributed to A Sjöberg.
Methodological studies on single meal food intake characteristics in normal weight and obese men and women.
METHOD: The eating behaviour of 19 normal weight males, 19 obese males, 19 normal weight females and 19 obese females was measured by means of VIKTOR, our version of the universal eating monitor. The total food intake, the duration of consumption, the rate of consumption, the relative rate of consumption and the subjective motivation to eat were measured during five homogenous lunch meals to analyse how these variables were related to body weight or to sex. Furthermore, the stability of the eating characteristics over the five eating occasions were tested with pre-defined criteria of stability. The predictive validity of the variables measuring subjective motivation to eat and forthcoming food intake was also tested. RESULTS: Men ate more food than women; normal weight men by eating for a longer time and obese men by eating faster. Females did not slow down the eating rate towards the end of the meals as much as males did. The obese subjects described themselves as having less motivation to eat prior to meals than normal weight subjects. CONCLUSIONS: Total stability, i.e. both relative and absolute stability, for all subjects was present for the eating variables intake of food and eating rate. Of the variables measuring subjective motivation to eat (desire to eat, hunger, fullness and prospective consumption) on visual analogue scales, only the variables desire to eat and prospective consumption predicted forthcoming food intake.
Adult↗
Continuous but not intermittent administration of growth hormone to hypophysectomized rats increases apolipoprotein-E secretion from cultured hepatocytes.
Hypophysectomy of female rats has been shown to decrease the serum levels of apolipoprotein E (apoE). Continuous but not intermittent administration of GH to hypophysectomized (HX) rats increases these levels to those of normal rats, indicating that the sexually dimorphic secretion of GH is important in the regulation of apoE metabolism. In this study, these effects of GH were further investigated by studying the biosynthesis and secretion of apoE from isolated hepatocytes. Hepatocytes were isolated from HX rats as well as from HX rats that had received hormonal treatment with T4 and cortisol (C) or T4 and C together with GH given either as two daily sc injections (GH x 2) or as a continuous infusion (GHc). Hypophysectomy decreased by 47% the amount of apoE present in the culture medium after a 4-h incubation. Treatment of HX rats with T4 and C alone or in combination with GH x 2 did not influence the amount apoE present in the medium, whereas treatment with T4, C, and GHc increased the amount of apoE to that of normal controls. The different levels of apoE in the medium was not due to differences in the disappearance of apoE, indicating that it was caused by changes in the rate of apoE secretion. Consistent with this, hypophysectomy decreased the rate of intracellular accumulation of apoE measured by incubation of the cells with [35S]methionine for 0, 8, and 20 min. Treatment with T4, C, and GHc increased the rate of accumulation, but T4, C, and GH x 2 had no effect. The differences in the initial rate of intracellular accumulation of apoE were not due to variations in apoE messenger RNA pools or to differences in the degradation of apoE at a step early in the secretory pathway. These results indicate that the differences in the initial rate of accumulation of apoE results from differences in the translational rate. The major amount of apoE that was secreted to the medium appeared in the high-density lipoprotein fraction, whereas small amounts were present in the very-low-density lipoprotein fraction (VLDL). Hypophysectomy decreased the amount of newly secreted apoE in the VLDL fraction. Only therapy with T4, C, and GHc could restore the normal distribution of apoE in the VLDL fraction. In conclusion, the results indicate that the secretory pattern of GH is involved in the regulation of the apoE secretion by influencing the rate of translation.
Animals↗
Insulin-like growth factor-I and growth hormone have different effects on serum lipoproteins and secretion of lipoproteins from cultured rat hepatocytes.
GH has previously been shown to regulate serum lipoprotein levels and hepatic secretion of apolipoprotein-B (apo-B) and apo-E in the rat. The aim of this investigation was to study a possible role of insulin-like growth factor-I (IGF-I) in this regulation. Adult female rats were hypophysectomized and treated with recombinant human IGF-I (1.25 mg/kg.day) as a sc continuous infusion for 7 days. The effects of IGF-I were compared with those of bovine GH, given either as a continuous sc infusion or as two daily sc injections. All hypophysectomized rats were given replacement therapy with L-T4 and cortisol. Serum IGF-I concentrations increased to similar levels as a result of treatment with bovine GH and IGF-I. There was no effect of IGF-I on serum concentrations of glucose or insulin, whereas GH, independent of its mode of administration, increased serum insulin concentrations. Food intake was not affected by treatment with IGF-I. IGF-I had no effect on serum concentrations of cholesterol or apo-E, whereas GH given twice daily decreased serum cholesterol concentrations, and a continuous infusion of GH increased serum apo-E concentrations. Serum triglyceride and apo-B concentrations increased markedly as a result of IGF-I treatment, whereas GH had no effect on serum triglycerides, but decreased serum apo-B concentrations. Hepatocytes were isolated from hypophysectomized rats treated with L-T4 and cortisol alone or in combination with IGF-I and kept in short term cultures. In this system, IGF-I had no effect on the incorporation of [3H]glycerol in triglycerides or the mass of triglycerides in the cells and medium. There was no effect of IGF-I treatment on the secretion of apo-E or apo-B. Moreover, there was no effect of IGF-I treatment on the relationship between newly synthesized and secreted apo-B 48 and apo-B 100, as determined by [35S]methionine labeling of the proteins. In conclusion, the previously observed effects of GH on serum lipoproteins and hepatic apolipoprotein secretion does not seem to be mediated via IGF-I, but IGF-I has its own unique effects on serum triglyceride and apo-B levels. The increases in serum apo-B and serum triglyceride concentrations after IGF-I treatment were not dependent on increased hepatic secretion of apo-B or triglycerides.
Animals↗
Purification of diacylglycerol:acyltransferase from rat liver to near homogeneity.
A method to isolate a protein related to the diacylglycerol:acyltransferase (DGAT) activity in rat liver microsomes has been developed. The microsomes were treated with sodium deoxycholate (DOC; 0.1 mg/mg protein) at a concentration of 1 mM, i.e., below the critical micellar concentration (CMC), to remove luminal and loosely bound proteins. Three percent of the DGAT activity and all of the acylCoA hydrolyse activity were present in the supernatant, i.e., among the extracted loosely bound proteins. The insoluble material, recovered as a pellet, was suspended in DOC (1.6 mg/ml and mg protein in the original microsomes), and subjected to multiple, short (1-2 sec) sonications. CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate; 5 mg/ml) was then added, and the sonication was repeated. The detergent-treated microsomal membranes were filtered through a 0.22-micron filter and chromatographed on a Superose 6 column from which the DGAT activity was recovered in a high molecular mass fraction. A monoclonal antibody that reacted with this fraction was raised and used in immunoaffinity experiments. This antibody removed 93 +/- 6% (mean +/- SD, n = 4) of the DGAT activity present in solution and 44 +/- 6% (mean +/- SD, n = 5) of the applied activity could be recovered after desorption. The antibody recognized a 60 kDa protein upon Western blot of rat liver microsomal proteins as well as of the DGAT-containing fraction from the Superose 6 column. A 60 kDa protein was highly enriched in the DGAT-containing retained fraction from the immunoaffinity chromatography. This 60 kDa protein reacted with the monoclonal antibody on Western blot. In addition to the 60 kDa protein, the retained fraction from the immunoadsorber contained a 77 kDa protein. This protein did not react with the monoclonal antibody on Western blots. Neither the 60 nor the 77 kDa protein reacted with antibodies to mouse immunoglobulins or showed any unspecific reaction with immunoglobulins.
Acyltransferases↗
Prevalence of carnitine depletion in critically ill patients with undernutrition.
The aim of this study was to evaluate to what extent secondary carnitine deficiency may exist based on the prevalence of subnormal carnitine status in patients with critical illness and abnormal nutritional state. Healthy control patients (n = 12) were investigated and compared with patients with possible secondary carnitine deficiency, ie, patients with overt severe protein-energy malnutrition (PEM, n = 28), postoperative long-term (greater than 14 days) parenteral glucose feeding (250 g glucose/d, n = 7), severe liver disease (n = 10), renal insufficiency (n = 7), and sustained septicemia with increased metabolic rate (n = 8). Nutritional status, energy expenditure, creatinine excretion, and blood biochemical tests were measured in relationship to free and total carnitine concentrations in plasma and skeletal muscle tissue, as well as urinary excretion of free and total carnitine. The overall mortality rate was 48% within 30 days of the investigation in study patients with the highest mortality in liver disease (90%). The hospitalization range was 14 to 129 days in study patients. Most study patients had lost weight (4% to 19%) and had abnormal body composition. Patients with liver disease, septicemia, renal insufficiency, and those on long-term glucose feeding had significantly higher than predicted metabolic rate (+25% +/- 3%), while patients with severe malnutrition had decreased metabolic rate compared with controls. Patients with liver disease had increased plasma concentrations of free (96 +/- 16 mumol/L) and total (144 +/- 27 mumol/L) carnitine compared with controls (45 +/- 3, 58 +/- 7 mumol/L, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Effects of growth hormone on apolipoprotein-B (apoB) messenger ribonucleic acid editing, and apoB 48 and apoB 100 synthesis and secretion in the rat liver.
Apolipoprotein-B 48 (apoB 48) and apoB 100 expression and the editing of apoB mRNA have previously been shown to be hormonally regulated in rat liver. We have investigated the effects of hypophysectomy and replacement therapy with T4, cortisol (C), and GH in vivo on the proportion of edited apoB mRNA in rat liver and cultured rat hepatocytes as well as the synthesis and secretion of apoB 48 and apoB 100 in cultured rat hepatocytes. Hypophysectomy decreased the proportion of edited apoB mRNA in intact liver from 62% in normal rats to 29% in hypophysectomized rats. Treatment of hypophysectomized rats with T4 and C did not influence the proportion of edited apoB mRNA, whereas treatment with GH, either alone or together with T4 and C, increased the proportion of edited apoB mRNA to the levels observed in normal rats. In cultured hepatocytes isolated from normal rats, the proportion of apoB 48 (percentage of total labeled apoB) was 78% and decreased to 40% in cells isolated from hypophysectomized rats. Treatment of hypophysectomized rats with T4 and C had no effect on the proportion of apoB 48 present in isolated cells, whereas it increased to 60% after treatment with GH together with T4 and C. The proportion of apoB 48 in the medium was affected by hypophysectomy and the various hormonal treatments in a similar way to that observed in the cells. Results from in vivo labeling experiments suggested that GH alone had the capacity to increase the percentage of apoB 48 in hypophysectomized rats. On the contrary, T4 and C was needed, in addition to GH, to increase the proportion of apoB 48 in isolated hepatocytes from hypophysectomized rats. Our results suggest that this discrepancy is due to a difference between the effect of GH alone on apoB mRNA editing in the intact liver and that in isolated hepatocytes. The total secretion of apoB into the cell culture medium was not affected by hypophysectomy and hormonal treatments of the rats. In conclusion, these results indicate that GH is involved in the regulation of editing of apoB mRNA and the proportion of apoB 48 synthesized and secreted in rat liver. Thus, our observations emphasize the importance of GH as a regulator of lipoprotein metabolism.
Animals↗
The assembly and secretion of apoB 100 containing lipoproteins in Hep G2 cells. Evidence for different sites for protein synthesis and lipoprotein assembly.
Pulse-chase studies combined with subcellular fractionation indicated that LpB 100 (i.e. the apoprotein B (apoB) 100 containing lipoproteins) was released to the lumen of the secretory pathway in a subcellular fraction enriched in smooth vesicles, and referred to as SMF (the smooth membrane fraction). The migration of SMF during gradient ultracentrifugation as well as kinetic studies indicated that the fraction was derived from a pre-Golgi compartment, probably the smooth endoplasmic reticulum (ER). Only small amounts of LpB 100 could be detected during these pulse-chase experiments in the subcellular fractions derived from the rough endoplasmatic reticulum (RER). SMF contained the major amount of the diacylglycerol acyltransferase activity present in the ER, while the major amount of membrane bound apoB 100 was present in the RER. Pulse-chase studies of the intracellular transfer of apoB 100 demonstrated the formation of a large membrane-bound preassembly pool in the ER, while no significant amount of apoB 100 radioactivity was present in the membrane of the Golgi apparatus. The maximal radioactivity of LpB 100, recovered from the ER or the Golgi lumen, was small compared with the radioactivity recovered from the ER membrane, indicating that the assembled LpB 100 rapidly leaves the cells. This in turn indicates that the rate-limiting step in the secretion of apoB 100 was the transfer of the protein from the ER membrane to the LpB 100 in the lumen. A portion of the intracellular pool of apoB 100 was not secreted but underwent posttranslational degradation.
Acetylglucosaminidase↗
Treatment of familial hypercholesterolaemia: a controlled trial of the effects of pravastatin or cholestyramine therapy on lipoprotein and apolipoprotein levels.
The efficacy and safety of a new, selective inhibitor of cholesterol synthesis, pravastatin, and the bile acid-binding resin, cholestyramine, were compared in a randomized, double-blind study of 120 patients with familial hypercholesterolaemia. After a run-in period of 8-10 weeks with assessment of dietary habits, the patients were treated with pravastatin + placebo, placebo + cholestyramine, or placebo alone. Active pravastatin therapy was initiated with 10 mg b.i.d. for 6 weeks, and was increased to 20 mg b.i.d. for the following 6 weeks. Cholestyramine was given at 24 g d-1, or the highest tolerable dose. After 6 weeks of therapy, serum total and LDL cholesterol levels were reduced by 17% and 21%, respectively, on pravastatin treatment, whereas the corresponding reductions with cholestyramine treatment were 24% and 30%, respectively. With an increased dose of pravastatin, serum and LDL cholesterol concentrations were reduced by 23% and 28%, respectively, after 12 weeks; the effect of cholestyramine was unchanged. HDL cholesterol levels increased in response to pravastatin, by 7% and 9% after 6 and 12 weeks, respectively. Concomitant changes in the concentrations of apolipoproteins B and AI were observed. Three patients discontinued the study because of side-effects: two subjects were treated with pravastatin and one was given placebo. The prevalence of side-effects (including laboratory abnormalities) was 35% for pravastatin, 30% for placebo, and 53% (significantly higher) for cholestyramine. We conclude that pravastatin, in a 40 mg daily dose, is as effective as cholestyramine in lowering LDL cholesterol in familial hypercholesterolaemia. Since the frequency of side-effects is higher with cholestyramine, pravastatin offers a promising alternative for the therapy of this genetic disease.
Adult↗
Studies on the assembly of apo B-100-containing lipoproteins in HepG2 cells.
The relationship between apoB-100 and the membrane of the endoplasmic reticulum (ER) has been studied by a combination of pulse-chase methodology and subcellular fractionation. HepG2 cells were pulse-labeled with [35S]methionine for 3 min and chased with cold methionine for periods between 0 and 20 min. ApoB-100 and albumin, present in the membrane as well as in the luminal content of the ER vesicles, were isolated after each chase period. The results indicated that apoB-100 was cotranslationally bound to the membrane of the ER, and from this membrane-bound form, was transferred to the lumen after a delay of 10-15 min. Albumin was, as could be expected for a typical secretory protein, cotranslationally sequestered in the lumen of the ER. Apo-B-100-containing lipoproteins present in the microsomal lumen were analyzed by ultracentrifugation in a sucrose gradient. ApoB-100 occurred on rounded particles in three density regions: (i) d 1.1065-1.170 g/ml (Fraction I), (ii) d 1.011-1.045 g/ml (Fraction II), and (iii) d less than 1.011 g/ml (Fraction III). Fraction I, isolated from cells cultured in the absence of oleic acid, contained a homogenous population of particles with a mean diameter of approximately 200 A. Fraction I isolated from cells cultured in the presence of oleic acid was slightly more heterogeneous and had a mean diameter of approximately 250 A. Fractions II and III had mean diameters of 300 and 500 A, respectively. Cholesterol esters and triacylglycerol were the quantitatively dominating lipid constituents of all three fractions. Pulse-chase experiments indicated that Fraction I contained the newly assembled lipoproteins. With increasing chase time, the apoB-100 radioactivity was redistributed from Fraction I to Fractions II and III, indicating that Fraction I is converted into Fractions II and III during the intracellular transfer. Particles corresponding to Fractions II and III were by far the most abundant lipoproteins found in the medium. The results presented support the possibility of a sequential assembly of apoB-100-containing lipoproteins.
Albumins↗
Mortality and cancer morbidity in workers exposed to sulphur dioxide in a sulphuric acid plant.
To evaluate the risk of non-malignant respiratory disease and tumours at exposure to sulphur dioxide, a retrospective cohort study was performed on a group of 400 male workers, employed for at least six months during the period 1961-1981, in a sulphuric acid factory. Since 1969, fairly extensive measurements have been performed in the respiratory zone of the workers. The median level of total dust, over the years, was 2.2 mg/m3 (time-weighted average), of respirable dust 0.6 mg/m3, of sulphur dioxide 3.6 mg/m3, and of arsenic 11 micrograms/m3. There was a significantly increased total mortality in the period 1961-1985. Applying greater than or equal to 5 years latency period there were 47 observed deaths, giving a standardized mortality rate (SMR) of 1.57 (P = 0.002). The increased mortality was due to violence and intoxication (observed 9, SMR = 2.83; P = 0.006) and cardiovascular disease (SMR = 1.51, P = 0.05). The total tumour morbidity was not increased (observed 17, SMR = 1.17, P greater than 0.5) and there was no rise of either non-malignant or malignant lung diseases. However, there was an increase of bladder cancer (observed 5, SMR = 4.36, P = 0.006).
Chemical Industry↗
Coumarin associated skin necrosis.
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Adult↗
[6 case reports of warfarin-induced skin necrosis].
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Adult↗
Acute and long-term airway hyperreactivity in aluminium-salt exposed workers with nocturnal asthma.
Nineteen young male workers exposed occupationally from 1975-1977 to inhaled particles of aluminium fluoride or sulphate at 2 plants, developed nocturnal wheezing and breathlessness with reversible airways obstruction after an average of 4 months employment. At standardized methacholine provocation tests (MPT), 17 of 19 workers with normal spirometry showed airway hyperreactivity with a fall of FEV1 of greater than or equal to 15% after 0.1% methacholine. We followed 15 initially asthmatic workers for 2-5 years with MPT. Mean TD 15% FEV1 in 11 workers did not change significantly after an average of 41 months of non-exposure. Six workers continuously exposed for 48 months also failed to change their TD 15% FEV1 MCh. In 1983, only one subject had returned to normal airway reactivity. We have no reason to suspect inducing agents other than aluminium salts.
Adult↗
Cancer incidence and exposure to iron oxide dust.
Iron oxides, particularly hematite, have been suspected for carcinogenic properties based on epidemiological observations and experimental data. This case-control (case-referent) study concerns a worker population with high exposure to dust of iron oxides, particularly hematite, and with some impurities of pentavalent arsenic and other metals. In spite of the high exposure levels no excess of cancer has been observed, either in the respiratory system or at other sites. It is suggested that earlier findings of respiratory cancers as possibly associated with iron oxides exposure might rather be due to other concomitant risk factors.
Adult↗