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Biomedical subjects

E Nilsson

Publications and source records attributed to E Nilsson.

At least 19 recordsLinked to original sources

Cereal fiber, calcium, and colorectal cancer.

Food intake during the preceding 15 years was evaluated in detail in 41 patients treated for colorectal cancer and an equal number of matched control subjects by means of a dietary history technique that permitted quantitation of nutrients. Dietary habits of the control group could be compared against two larger groups of 371 hospital control and 430 population control subjects. Patients with cancer, who were interviewed after complete recovery from surgery, consumed more fat, protein, and carbohydrates, and thus more energy, than control subjects although these differences were not statistically significant. Per unit energy, the habitual diet of patients with cancer contained less cereal fiber (P less than 0.001), less riboflavin (P less than 0.05), less calcium (P less than 0.05), and less phosphorus (P less than 0.05) than the diet of the control subjects. A high intake of either cereal fiber, total fiber, calcium, and phosphorus in relation to energy intake was found to be associated with a reduced risk ratio of colorectal cancer. For colon cancer separately, a high intake of calcium and cereal fiber was associated with a reduced risk ratio. For rectal cancer, a high intake of total fiber and cereal fiber was associated with a reduced risk ratio. High alcohol consumption correlated with an increased risk ratio. These data are compatible with previous Scandinavian studies relating food consumption to the incidence and mortality of colorectal cancer.

Aged

T cell receptor diversity and activation markers in the V delta 1 subset of rheumatoid synovial fluid and peripheral blood T lymphocytes.

In the present study we have characterized the gamma/delta T cell receptor (TcR) population in synovial fluid (SF) and peripheral blood (PB) of patients with chronic inflammatory arthritis. By double staining we have shown that (a) synovial V delta 1+ cells have a high expression of activation markers CD45R0 ("memory cells") and HLA-DR as compared to PB, indicating a preactivated population of V delta 1-carrying T cells in vivo and (b) interleukin 2-induced expansion of synovial cells yields a high proportion of gamma/delta in most samples expressing predominantly the V delta 1 TcR. Junctional sequence analysis of the TcR delta chain from interleukin 2-expanded PB cell lines demonstrated a polyclonal V delta 1 population in three out of three samples. In SF cell lines three out of four samples were polyclonally expanded. In SF from one patient, however, a limited repertoire of expressed V delta 1 genes was found. Altogether, our data demonstrate the presence of preactivated V delta 1-expressing cells in the synovial compartment. This V delta 1 population is predominantly polyclonal, except in one patient where oligoclonally expanded V delta 1 cells were detected.

Antigens, CD

Integrins and other adhesion molecules on lymphocytes from synovial fluid and peripheral blood of rheumatoid arthritis patients.

Cell and matrix adhesion of lymphocytes participates in homing, migration and accumulation of these cells in inflamed tissues as well as in the generation of immune and inflammatory responses. In inflamed joints of rheumatoid arthritis (RA) patients, lymphocytes accumulate in the synovial membrane and the synovial fluid. In the present study we have analyzed the expression of integrins and other adhesion molecules in synovial fluid lymphocytes (RA-SFL) and paired peripheral blood lymphocytes (RA-PBL) from 21 RA patients by immunofluorescence flow cytometry. We have also investigated the expression of these adhesion molecules on peripheral blood lymphocytes obtained from 13 sex- and age-matched healthy controls (CO-PBL). RA-SFL, which consisted mostly of T cells, showed higher expression of the integrin subunits beta 1 (CD29), VLA-1 alpha, -3 alpha, -4 alpha, -5 alpha and -6 alpha when compared to RA-PBL. In turn, RA-PBL showed lower expression of these molecules than CO-PBL. The expression of the immunoglobulin-related molecules CD2, CD54 (ICAM-1) and CD58 (LFA-3) was higher on RA-SFL when compared to RA-PBL or CO-PBL, and similar results were obtained with the beta 2 integrin subunits CD11a and CD18. In contrast, L-selectin (LECAM-1) and ICAM-2 were expressed at much lower levels on RA-SFL than on RA-PBL or CO-PBL. CD44, a receptor for hyaluronic acid and collagen, was expressed by most RA-SFL, RA-PBL and CO-PBL cells but at higher density on RA-SFL. The results indicate that RA-SFL express a distinct array of adhesion molecules, similar to the one of memory T lymphocytes. This characteristic phenotype may contribute to the lymphocytic infiltration of the synovium and to the pathogenesis of RA.

Adult

Effect of the selective MAO-A inhibitors brofaromine, clorgyline and moclobemide on human platelet MAO-B activity.

MAO-B activity was compared in healthy volunteers following oral treatment with clinically effective doses of the selective MAO-A inhibitors brofaromine (100 mg q.d. for 14 days), moclobemide (150 mg t.i.d. for 14 days) and clorgyline (5 mg t.i.d. for 10 days). Brofaromine and clorgyline did not alter platelet MAO activity. Following moclobemide treatment, MAO-B activity was reduced by 32% (p less than 0.05). It recovered during the 5 subsequent days after discontinuation of treatment. These results confirm earlier findings. The explanation for this finding may be that metabolites of moclobemide are active inhibitors of MAO-B.

Adult

The possible role of Coxsackie A and echo viruses in the pathogenesis of type I diabetes mellitus studied by IgM analysis.

IgM antibodies to Coxsackie B virus (CBV) have recently been observed in the serum of a relatively high proportion of children with newly diagnosed insulin-dependent diabetes mellitus (IDDM). In the present study, 108 IDDM patients below the age of 15 years, diagnosed during the period 1976 to 1985, were investigated at the onset of their disease by mu-antibody-capture radioimmunoassay (RIA) of IgM against seven different enterovirus antigens, namely virions of CBV serotypes 1-5 (CBV 1-5) and procapsids of CBV 3 and CBV 5. As has been shown the RIAs with virions give type-specific or narrow type-specific reactions, whereas procapsids react with IgM against both homotypic and heterotypic enteroviruses. The annual frequency of IgM against virions varied between 15 and 76% (mean 38%). IgM against CBV3 and CBV2 predominated, but IgM against the other serotypes was also observed. When procapsids were used as antigen, the frequency of IgM varied between 11 and 86% (mean 63%). With virions and procapsids, the corresponding variation was 44-100% (mean 70%). The total number of patients exhibiting virion-IgM was 41, whereas procapsid-IgM alone [indicating an infection with Coxsackie A virus (CAV) and/or echo virus (EV)] was detected in 36 patients. For 2 of the years, samples of serum from control groups were included. These showed a significantly lower frequency of IgM in both the virion and the procapsid RIAs. It is concluded that not only infection with CBV but also that with other enteroviruses, such as CAV and/or EV, may be involved in the pathogenesis of IDDM in children.

Adolescent

Effects of ethanol on the chemotactic peptide-induced second messenger generation and superoxide production in polymorphonuclear leukocytes.

The generation of oxygen radicals by polymorphonuclear leukocytes (PMNL) plays a pivotal role for host defense. Since ethanol reduced FMLP- but not PMA-induced superoxide ion (O2-) formation by PMNL, the effects of ethanol on second messenger systems in PMNL were studied. FMLP induced a biphasic rise in cytosolic calcium concentrations, [Ca2+]i. Ethanol treatment abolished the second phase (believed to reflect Ca2+ influx), an effect also observed in PMNL treated with La3+ or suspended in Ca(2+)-free buffer. The FMLP-induced inositol trisphosphate generation was unaffected by ethanol, whereas diacylglycerol formation was, as expected, markedly reduced. Propranolol, an inhibitor of diacylglycerol formation from phosphatidic acid, caused a prolonged transmembrane influx of Ca2+ and partially reversed the inhibitory effect of ethanol on FMLP-induced O2- production. Thus, the ability of ethanol to inhibit FMLP-induced O2- generation in neutrophils seems to be due to both impaired influx of Ca2+ across the plasma membrane and reduced phospholipase D-mediated generation of phosphatidic acid.

Calcium

Muscle composition in relation to age and sex.

1. A method is described enabling the determination of fat, water, electrolytes, protein, DNA, RNA and total creatine in a single sample of human muscle obtained by the percutaneous needle-biopsy technique. The amino acid content can also be analysed in the same muscle sample. 2. Fifty healthy subjects were studied: 29 between 19 and 40 years of age, 11 between 41 and 60 years of age, and 10 between 61 and 85 years of age. The two groups aged less than 60 years showed only marginal differences in muscle composition, whereas the highest age group showed increases in muscle fat content in relation to tissue weight and decreases in alkali-soluble protein content in relation to both tissue weight and tissue DNA content. Also, potassium, magnesium, total creatine and RNA contents were decreased in this age group when related to tissue DNA content. When alkali-soluble protein was used as a reference base, only magnesium content was decreased. 3. A comparison was also made between female (n = 23) and male (n = 18) subjects in the age groups below 60 years. Differences observed included a higher fat content in female muscle, and an increase in total creatine content in relation to tissue weight. The alkalisoluble protein content was lower per muscle cell in the females when calculated on the basis of DNA content. 4. The results show that in the assessment of muscle constituents, age and sex must be taken into account.

Adult

Ethanol impairs certain aspects of neutrophil adhesion in vitro: comparisons with inhibition of expression of the CD18 antigen.

Since ethanol impairs polymorphonuclear leukocyte (PMNL) delivery to inflammatory sites, the effect of ethanol on PMNL adhesiveness was studied in vitro. Ethanol inhibited PMNL aggregation induced by formylmethionylleucylphenylalanine (FMLP) but not by phorbol myristate acetate (PMA), whereas responses to both stimuli were abolished by treating PMNL with monoclonal antibody 60.3 (against the adhesion protein CD18). This antibody also abrogated spontaneous and FMLP-stimulated PMNL adhesion to plastic, whereas ethanol reduced spontaneous but not FMLP-induced adherence. Chemotaxis in Boyden or agarose systems was not diminished by ethanol, but high concentrations of MAb 60.3 inhibited migration under agarose. Nonetheless, upregulation of cell surface expression of CD18 (assessed by immunofluorescence flow cytometry) induced by FMLP or PMA was similarly reduced by ethanol. Thus, ethanol inhibited only certain of PMNL adhesion, and although the stimulated up-regulation of CD18 expression was reduced it is unlikely that ethanol effects were mediated only by this inhibition.

Antigens, CD

On the binding of tumor necrosis factor (TNF) to heparin and the release in vivo of the TNF-binding protein I by heparin.

Tumor necrosis factor (TNF), a protein released by activated macrophages, is a central mediator of the host response to infection and inflammation. The TNF-binding protein I (TNF-BP-I) is a soluble fragment of the p60 transmembrane TNF receptor and an antagonist to TNF. The level of serum TNF-BP-I was found to be increased in patients with renal insufficiency as a result of a decrease in the glomerular filtration rate. During hemodialysis of patients with renal failure there was a rapid but transient increase in serum TNF-BP-I. This increase was found to be caused by heparin given before dialysis and a similar dose-dependent response to heparin was observed also in healthy individuals. The finding of a repeated release of TNF-BP-I into the circulation with intermittent injections of heparin indicates that TNF-BP-I is present both in a storage pool and in a circulating pool. The mechanism for the heparin-mediated release of TNF-BP-I was not explained; TNF-BP did not show affinity for heparin. On the other hand, TNF was found to have affinity for heparin and it could also be dissociated from heparin by TNF-BP-I. It is suggested that heparin-like molecules of the extracellular matrix can retain TNF in physical proximity with target cells and restrict the actions of TNF and protect against systemic harmful manifestations.

Carrier Proteins

T lymphocyte subpopulations in synovial fluid of patients with rheumatic disease.

The proportion of T lymphocytes with receptors for the Fc portion of IgG (TG cells) of IgM (TM cells) was determined in synovial fluid and blood of 16 patients with various rheumatic diseases including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. The percentage of TG cells was low in all synovial fluid samples, whereas in the patients' blood the percentage was higher than or equal to the level found in the blood of healthy subjects. Eight patients also had a lower level of TM cells in synovial fluid as compared to the percentage found in the blood of healthy donors. In the patients' blood the percentage of TM cells was usually within the normal range. Thus the proportion of T cells lacking either receptor (Tnull cells) was higher in synovial fluid than in blood. This pattern of low TG cell and high Tnull cell percentages was found in the synovial fluid of patients with various rheumatic diseases and thus seems to be a general feature of chronic inflammatory joint exudates.

Arthritis, Rheumatoid

Leg temperature profiles with a simplified thermographic technique in the diagnosis of acute venous thromboses.

A simplified thermographic technique has been developed to provide continuous leg temperature profiles by manual scanning with a noncontactile infrared radiation transducer connected to a linera potentiometer for determination of the transducer position. The clinical value of the technique in the diagnosis of acute venous thromboses has been estimated in seventy patients and thirty controls, using plethysmography and phlebography as methods of reference. The thermographic diagnosis was based on side differences in temperature levels within different segments of the limbs, as calculated from the temperature profiles by means of planimetric technique. Standardized temperature profiles from the medial side of the limbs were found to demonstrate a side difference above the reference level in fifty-seven of fity-nine patients with acute venous thromboses, which means a diagnostic sensitivity corresponding to that of conventional thermography. Skin temperature profiles were superior to plethysmography, particularly in the diagnosis of thromboses located distally. Falsely positive results were obtained, as expected, in some cases of varicose veins or acute arthritis and skin infections. The presented type of thermography has obvious qualifications as a screening method in the early diagnosis of acute venous thromboses, being far less expensive but never the less more suited for objective numerical analyses and evaluation than conventional thermography with scanning cameras.

Acute Disease

Physico-chemical modification of lidocaine uptake in rat lung tissue.

The uptake of lidocaine, methyllidocaine, bupivacaine, etidocaine was studied in rat lung slices at different pH-values. The accumulation of the quaternary analogue, methyllidocaine, was not changed in the pH interval 7.0--8.0. The uptake of the three other substances was about 3--4 times lower at pH 7.0 than at pH 8.0. The rank order of distribution at a fixed cation/base ratio was bupivacaine greater than etidocaine greater than lidocaine. Interactions between lidocaine and other substances were studied in lung slices and in isolated perfused lungs. Bupivacaine and nortriptyline counteracted the accumulation of 14C-lidocaine in lung slices in a dose-dependent manner. Nortriptyline was more effective than bupivacaine. In isolated perfused lung, bolus injections of nortriptyline and lidocaine rapidly displaced 14C-lidocaine from the tissue. In this study we suggest that the base form of local anaesthetics accumulate in the lung tissue, while the cationic form binds to accessible binding sites in the cell membranes.

Animals

Transport and binding of lidocaine by lung slices and perfused lung of rats.

The accumulation of radioisotopically labelled lidocaine was investigated in lung slices and perfused lungs of rats. Lidocaine was taken up by rat lung slices incubated in an oxygenated physiological solution (pH 7.4) at 37 degrees. 14C-lidocaine accumulated in lung slices to a much greater extent than did 3H-sucrose, and the lidocaine space was approximately 7 times that of the extracellular space. No metabolism of lidocaine took place during the incubation period. The accumulation of lidocaine was inhibited by low temperature, while anaerobic conditions had no inhibitor effect. The uptake of lidocaine (0.028 mM) was slightly antagonized by high concentrations of Ca2+ (10 mM). The isolated perfused lung model was used for studying the pulmonary absorption of lidocaine from the vascular bed. Lidocaine was rapidly extracted from the perfusion solution and the drug appeared to accumulate in at least two compartments. It seems that in the rat lung a portion of the lidocaine taken up had accumulated within the cells, while some of it may be fixed to the cell surfaces.

Animals

Mitogenicity of Mycoplasma fermentans for human lymphocytes.

The in vitro stimulation response of human lymphocytes to Mycoplasma fermentans was examined. M. fermentans stimulated DNA synthesis in blood lymphocytes from all of 20 healthy subjects examined. Only one of these subjects had complement-fixing antibodies to M. fermentans. Lymphocytes from 21 of 22 adenoids and from 1 spleen were also stimulated to DNA synthesis by M. fermentans. The organism induced DNA synthesis in both B and T lymphocytes from adenoids and spleen and preferentially in T lymphocytes from blood. M. fermentans was shown to activate adenoid lymphocytes to non-amtogem-specific antibody secretion demonstrable by a hemolytic plaque assay. It is concluded that M. fermentans can have a mitogenic effect on both B and T lymphocytes.

Antibodies, Bacterial