Metabolic fate of CGS 8216, a benzodiazepine receptor antagonist, in rat and in man.
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Administration, Oral↗
Biomedical subjects
E Nilsson
Publications and source records attributed to E Nilsson.
Efficacy of and adverse effects of disopyramide. Comparison of capsules, controlled release tablets and placebo in patients with chronic ventricular arrhythmias.
The efficacy of disopyramide compared to placebo for exercise induced ventricular arrhythmias was tested in a double-blind randomized controlled clinical trial with cross-over design in 14 patients with coronary heart disease. Disopyramide was given as ordinary capsules (q.i.d.) or as a slow release preparation (b.i.d.) in a total dose of 600 mg per day. The placebo preparations were identical looking capsules and tablets. Each treatment period lasted one week. Efficacy was assessed by a standardized exercise test on a bicycle ergometer and a 6-h Holter monitoring at the end of each period. Plasma levels of disopyramide, measured in conjunction with exercise test, fell within therapeutic range, with a mean value of 7.9 and 8.9 mumol/l for capsules and slow release tablets, respectively. Disopyramide gave a marked and significant reduction of ventricular ectopic beats both at rest and during and after exercise. There was also a significant decrease in the number of ectopic beats recorded on tape during treatment periods compared to during placebo periods. There were no differences between the two preparations with respect to antiarrhythmic effect. Only mild side-effects, mainly mild anticholinergic symptoms, similar for both preparations were reported. No significant cardiovascular changes (heart rate and blood pressure response) were observed.
Aged↗
Immunoregulatory function of T8 and T4 cells from synovial fluid of patients with chronic arthritis.
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Antibody Formation↗
Plasma catecholamines following nursing procedures in a neonatal ward.
Plasma catecholamines (CA) were determined in arterial blood from infants in a neonatal ward before and after various management procedures. Special care led to a 60% increase in plasma noradrenaline levels (P less than 0.02) whereas the adrenaline concentrations were not significantly affected. CA levels tended to be slightly higher after heel prick and gavage feeding than before, but the differences were not significant.
Blood Pressure↗
Density of the microflora in hand eczema before and after topical treatment with a potent corticosteroid.
Twenty patients with hand eczema were studied with the use of quantitative bacteriologic cultures before and after successful topical treatment with a potent corticosteroid. One sample was taken from the most pronounced eczematous lesion, a second from skin affected with only erythema, and a third from clinically normal skin. Before quantitative bacteriologic analysis, the different species were combined into three main groups: Staphylococcus aureus, other aerobes, and anaerobes. Before treatment, S. aureus colonized the most pronounced eczematous lesion in eighteen of twenty patients and exceeded 10(5) cfu/cm2 in fifteen of twenty patients. The geometric mean count of S. aureus before treatment was significantly higher in eczema (10(4.8) cfu/cm2) than in erythema (10(3.4) cfu/cm2) and significantly higher in erythema than in normal skin (10(1.7) cfu/cm2). The density of other aerobes and anaerobes was similar in the three sampling sites. After treatment, the mean count of S. aureus was significantly reduced at all three sampling sites, and the densities became equal. Treatment did not affect the mean count of other aerobes or anaerobes.
Administration, Topical↗
Plasma lipoproteins and fatty acid composition during a moderate eicosapentaenoic acid diet.
The effect of a diet rich in marine fatty acids, especially eicosapentaenoic acid, on plasma lipids (total plasma cholesterol, HDL cholesterol, total triglycerides and apolipoproteins A and B) and fatty acid composition in plasma phosphatidylcholine (PC) was studied in 10 healthy men. They were maintained for 11 weeks on their normal diet which was partly replaced by 150-200 g of fatty fish per day. In the same individuals this diet had previously caused a delay in primary haemostasis and a decrease in platelet aggregability similar to that caused by acetylsalicylic acid, a known inhibitor of thromboxane A2 formation. Apart from its effect on haemostasis, the fish diet substantially reduced serum triglycerides (by 43%, p less than 0.01) but caused no changes in total plasma or HDL cholesterol or apolipoproteins A and B. After three weeks on the diet the proportion of plasma PC omega-3 polyunsaturated fatty acids increased (C20:5 and C22:6) and omega-6 fatty acids decreased (C18:2 and C20:3). The relative plasma PC content of arachidonic acid was unaffected throughout. These alterations in plasma PC fatty acid composition were principally in accordance with those seen in platelet membrane PC. There was a linear correlation between the content of omega-3 and of omega-6 fatty acids in plasma PC with that of platelet PC as well as in predominate individual fatty acids of the two series. Six weeks after the volunteers had resumed their usual diet, total triglycerides and the fatty acid composition of plasma PC had returned to the original state.
Adult↗
T-cell helper activity and B-cell function of synovial and blood lymphocytes from patients with rheumatoid arthritis or other forms of chronic arthritis.
The helper effect of T cells on B-cell immunoglobulin (Ig) responses induced by pokeweed mitogen (PWM) or purified protein derivative of tuberculin (PPD) was studied in lymphocytes from synovial fluid (SF) and blood of nine patients with rheumatoid arthritis (RA) and eight patients with other forms of chronic arthritis. In PWM cultures the helper effect of SF T cells on Ig responses (IgG, IgM, IgA) of autologous and allogeneic blood B cells was lower than that of blood T cells (P less than 0.01). This decrease was more pronounced in patients with RA than in patients with non-RA. In PPD cultures no significant difference was found between the helper effect of SF T cells and blood T cells on the Ig responses of allogeneic blood B cells or on the IgG response of autologous blood B cells, whereas the helper effect of SF T cells on the IgM and IgA responses of autologous blood B cells was decreased. The Ig responses to PWM or PPD in cocultures of autologous blood B and T cells were not significantly different between patients and healthy controls. The PWM- and PPD-induced Ig responses of SF B cells were lower than those of blood B cells when cocultured with autologous blood T cells. SF B cells produced IgG but usually little IgM and IgA. Thus there was a dysfunction of SF B cells and of SF T cells in a PWM-driven system, but a fairly good helper function of SF T cells in a PPD-driven system.
Adult↗
Immunoregulatory function of T8 and T4 cells from synovial fluid and blood of patients with rheumatoid arthritis or other forms of chronic arthritis.
The suppressor effect of synovial fluid (SF) T8 cells and blood T8 cells on the pokeweed mitogen (PWM)-induced T4 cell-dependent immunoglobulin production of autologous blood B cells was studied in nine patients with chronic rheumatic diseases (six patients with rheumatoid arthritis (RA), one patient with juvenile RA, and two patients with other forms of chronic arthritis). The suppressor effect of SF T8 cells was of the same magnitude as that of equal numbers of blood T8 cells from patients and healthy controls. However, the relative number of T8 cells was higher among SF T cells than among blood T cells in several cases. Good synovial T8 cell suppression was also demonstrated in coculture experiments where SF T4 cells and B cells were used. In PPD (purified protein derivative of tuberculin)-stimulated cultures the suppressor effect of SF T8 cells as well as of blood T8 cells from patients and controls was lower than it was in PWM-stimulated cultures. In most patients SF T4 cells showed a much better PWM-induced helper function than did non-fractionated SF T cells. Thus the poor PWM induced helper effect of non fractionated synovial T cells was in some cases mainly due to the suppressor effect of T8 cells, whereas in some cases there was also a deficient helper function of synovial T4 cells.
Adult↗
Characterization of brain calpains.
A new, simple one-step procedure [Karlsson et al. Biochem. J. 231, 201-204 (1985)] for the separation of calpains I and II was used prior to the characterization of these enzymes from rabbit brain, using alkali-denatured casein as the substrate. Enzyme activity was dependent on Ca2+ ions and free-SH groups and was maximal around pH 7.4. Incubation of calpains I and II with Ca2+ in the absence of substrate led to a rapid loss of enzyme activity. Enzyme activity was linear at room temperature and millimolar Ca2+ concentrations. However, when incubation of calpain I was performed with micromolar Ca2+ concentrations at room temperature proteolytic activity exhibited a lag period of approximately 10 min. This activation period was not as evident with calpain II.
Animals↗
Lung mechanics of the guinea-pig isolated perfused lung.
In the isolated perfused guinea-pig lung, lung resistance (RL) and dynamic compliance (CDYN) as well as flow, pH, PO2 and PCO2 of the perfusate were recorded. The baseline values were stable up to 2.5 h. Mean values (+/- SEM) for RL and CDYN were 0.36 cm H2O ml-1 s-1 +/- 0.04 and 0.27 ml cm-1 H2O +/- 0.02, respectively, which agree with in vivo values reported for unanaesthetized guinea-pigs. The pH was always slightly raised and the PCO2 always lowered in the effluent compared to the inflowing medium (P less than 0.001), indicating that the lung had an operative ventilation. Intravascularly administered acetylcholine, histamine and adenosine caused reproducible dose-dependent bronchoconstrictions recorded as increased RL and decreased CDYN. It is noteworthy that adenosine in this model and in vivo consistently produced bronchoconstriction which is in contrast to findings in other in vitro airway preparations. We conclude that this isolated perfused guinea-pig lung preparation has stable in vivo-like characteristics offering interesting possibilities for combining studies of respiratory effects with, for example, metabolism, pharmacokinetic and vascular reactivity studies.
Acetylcholine↗
Effects of recombinant tumor necrosis factor on proliferation and differentiation of leukemic and normal hemopoietic cells in vitro. Relationship to cell surface receptor.
The clonogenic growth of myeloid leukemia cell lines was inhibited by recombinant tumor necrosis factor (rTNF) at 1-15 pM concentration. However, wild type (promyelocytic) HL-60 cells were highly resistant to growth inhibition, but responded with differentiation into monocyte-like cells at 100 pM rTNF. The clonogenic growth of fresh acute myeloid leukemia cells was inhibited by 50% at approximately 15 pM rTNF. The growth of normal granulocyte-macrophage progenitors (CFU-GM) was also inhibited (by 50 pM rTNF), as was the growth of erythroid progenitors (BFU-E) (by 150 pM rTNF). A synergistic antiproliferative effect was demonstrated between rTNF and recombinant interferon-gamma. Use of radioiodinated rTNF enabled us to detect 1,500-2,100 binding sites on myeloid cell lines at 4 degrees C with Kd of approximately 300 pM. At 37 degrees C, the transfer of bound ligand to lysosomes was followed by degradation, inhibited by NH4+. No correlation was observed between the number of binding sites or affinity at 4 degrees C and antiproliferative response to the addition of rTNF.
Cell Differentiation↗
The importance of anamnestic information of atopy, metal dermatitis and earlier hand eczema for the development of hand dermatitis in women in wet hospital work.
By means of a prospective study design and multivariate regression analyses we have studied the relative importance of atopy, metal dermatitis and earlier hand eczema as risk factors for the development of hand eczema in women during 20 months of "wet" hospital work. The population consisted of 1857 women. The prevalence of hand eczema during the observation period was 41%. The risk of developing hand eczema was calculated as predicted relative odds ratios. The interrelationship of the risk factors was analysed. A summarized description of this analysis shows that a history of earlier hand eczema increased the odds by 12.9 times, a history of metal dermatitis by 1.8 times and atopic dermatitis and atopic mucosal symptoms by 1.3 times. Thus a history of earlier hand eczema seems of crucial importance for the occurrence of hand eczema in women in 'wet' hospital work. Our hypothesis is that a history of earlier hand eczema may be considered a major indicator of a skin vulnerability factor predisposing the individual to hand eczema. If the hypothesis is true, this factor may be present approximately in one half of the subjects with atopic dermatitis, in one fourth of the subjects with atopic mucosal symptoms and in one fifth of the non-atopics.
Asthma↗
Pancreatic trauma in a defined population.
In a 20-year period, 378 of a 390,000 population were laparotomized following abdominal trauma, and pancreatic injury was found in 27. Together with two nonsurgically treated patients, these gave an average annual incidence of 0.4 cases of pancreatic trauma/100,000 population. Ten of the injuries occurred in the first and 19 in the second decade of the study. The cause was traffic accident in 18 cases and penetrating wound in only two. The patients' median age was 17 years, and 23/29 were males. The pancreatic injury was the only important intraabdominal lesion in 17 patients, but 12 had associated, potentially lethal lesions. The main pancreatic duct was injured in 11/29 patients, most commonly in those with impaired circulation on admission. Six patients died, 5/11 with, and 1/18 without injury to the main pancreatic duct. Mortality was also related to defective preoperative and intraoperative diagnosis. Clinical recognition of isolated pancreatic injury is difficult, as pain and tenderness may be initially minimal. In two of the six fatal cases and four of the 11 with injured main pancreatic duct, the abdominal status was first judged to be normal.
Adolescent↗
T8 cell suppression of antigen- and mitogen-induced T4 cell dependent immunoglobulin production.
The suppressor effect of T8 cells on antigen-induced, as compared to pokeweed mitogen-induced, T4 cell dependent immunoglobulin (Ig) production by B cells of healthy subjects was studied. The antigens used were purified protein derivative of tuberculin (PPD) and tetanus toxoid (TT). The suppressor effect of T8 cells on IgG, IgM and IgA responses in co-cultures of T4 cells and B cells was significantly stronger in the pokeweed mitogen driven system than in PPD- and TT-driven cultures under the same experimental conditions.
Adult↗
Individual and environmental risk factors for hand eczema in hospital workers.
Individual and environmental risk factors in hand eczema have been investigated in a prospective cohort study of 2452 newly employed hospital workers with a follow-up time of 20 months. Current hand eczema was analyzed in 142 wet hospital workers from this cohort with respect to the etiologic importance of irritants, allergens and contact urticants. The density of the microflora and the effect on the microflora of topical treatment with a potent corticosteroid were studied in 20 patients with hand eczema. 'Wet' hospital work was found to increase the odds of developing hand eczema only twice compared to 'dry' office work. Nursing children under four years old and the lack of a dish-washing machine significantly increased the risk of contracting hand eczema. Unfavourable combinations of these domestic factors increased the risk as much as wet work. A history of atopic dermatitis approximately tripled the odds both in wet as well as in dry work. Histories of earlier hand eczema (HHE), metal dermatitis (HMD) and of atopy were analyzed as risk factors for hand eczema in 1857 women in wet work. HHE increased the odds by a factor of 12.9 and created a subdivision of the population into high risk individuals and normal risk individuals. HHE was found in half of the subjects with atopic dermatitis, in one quarter of the subjects with atopic mucosal symptoms and in one fifth of the non-atopics. A HMD increased the odds by a factor of 1.8. This increase was seen as a high risk level in subjects with HHE and as a normal risk level in subjects with no HHE. A history of atopic disease as a complement to information about HHE and HMD increased the odds by another 1.3 times. The predicted probability of developing hand eczema ranged from 91% in subjects with a combination of HHE, HMD and atopy to 24% in subjects with none of these risk factors. Subjects with AD were found to suffer a more severe form of hand eczema with significantly higher figures for medical consultation, sick-leave, termination due to hand eczema, early debut, permanent symptoms and vesicular lesions. Amongst the patients investigated for current hand eczema high risk individuals were overrepresented. It was claimed in 92.3% of the cases that trivial irritant factors had elicited the current episodes of hand eczema. In 35% of the cases the exposure to the irritant took place largely at home.(ABSTRACT TRUNCATED AT 400 WORDS)
Dermatitis, Occupational↗
Extracorporeal elimination of carbon dioxide using a surface heparinized vein-to-vein bypass system.
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Animals↗
T lymphocyte-derived differentiation-inducing factor inhibits proliferation of leukemic and normal hemopoietic cells.
A differentiation-inducing factor (DIF) for the promyelocytic HL-60 cell line is constitutively produced by the malignant T lymphocyte line HUT-102. DIF was highly purified from HUT-102-conditioned media by means of diethylaminoethanol (DEAE)-chromatography, gel chromatography, and high-resolution, ion-exchange chromatography on a MonoQ column and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In addition to inducing differentiation of wild-type HL-60 cells, resulting in secondary inhibition of growth, DIF, at a tenfold lower concentration, inhibited the growth of some clones of the monoblastic U-937 cell line as well as that of subclones of HL-60. The latter effect was most likely a primary growth inhibition and not secondary to differentiation; 50% inhibition of clonogenic growth in agar was seen at approximately 1.0 pmol/L of DIF. In addition, the clonogenic growth of fresh leukemia cells from 10 of 12 patients with acute myeloid leukemia (AML) was inhibited with 50% inhibition at approximately 10 pmol/L of DIF. The growth of normal granulocyte-macrophage colonies was inhibited at a similar concentration, whereas early erythroid colonies were much more resistant. DIF and interferon-gamma (gamma-IFN) were shown to be separate molecules inasmuch as a neutralizing antibody for gamma-IFN did not abolish the DIF effect. The differentiation effect on wild-type HL-60 and the proliferation inhibitory effect on leukemic and normal myeloid cells cochromatographed through all purification steps suggest that both activities are exhibited by identical polypeptides. DIF may have a role in regulating normal hemopoiesis. The growth inhibitory effect of DIF and the ability to induce differentiation of some leukemia cells may suggest a clinical utility in the treatment of leukemia.
Cell Differentiation↗
A simple one-step procedure for the separation of calpain I, calpain II and calpastatin.
The soluble fraction from rabbit brain was adsorbed on a column of phenyl-Sepharose. By applying a linear gradient with decreasing salt concentration and increasing pH, it was possible to separate calpain I and calpain II from each other and from the endogenous inhibitor calpastatin. Both enzymes were capable of degrading endogenously labelled neuronal proteins, including slowly axonally transported soluble proteins and rapidly transported membrane-bound proteins, as well as casein.
Calcium↗