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Biomedical subjects

N Grunnet

Publications and source records attributed to N Grunnet.

At least 145 records · Page 8Linked to original sources

Lymphocyte transformation tests and subpopulations of lymphocytes in a population-based material of atopic dermatitis in twins.

Lymphocyte function and lymphocyte subpopulations in the peripheral blood have been studied in a population-based material of 47 twins with atopic dermatitis (AD) (31 with a history of AD, 10 with mild AD, and 6 with moderate AD) and in 47 age- and sex-matched non-atopic control twins. Lymphocyte transformations to phytohaemagglutinin, concanavalin A (Con A), pokeweed mitogen, and purified protein derivative of tuberculin were investigated. Lymphocyte subpopulations were characterized by EAET rosettes and the monoclonal antibodies OKT3, OKT4, and OKT8. None of these in vitro tests showed any statistically significant differences between patients and controls. In the rather few individuals with moderate AD there was a statistically insignificant tendency to a decreased Con A stimulation in suboptimal concentration and a reduction of the OKT8+ cells. However, there were definitely no alterations in the immunological variables between patients with a history of AD and controls. Our results indicate that the investigated variables could be related to disease activity. We suggest that they represent epiphenomena rather than pathogenetic mechanisms of importance for the development of AD.

Adolescent↗

Adult respiratory distress-like syndrome during hemodialysis: relationship between activation of complement, leukopenia, and release of granulocyte elastase.

Twelve patients with terminal uremia (8 females and 4 males) treated with chronic maintenance hemodialysis, were extensively studied during two successive dialyses with alternate use of either a Cuprophan (CP) based membrane, or a Polycarbonate (PC) membrane. Arterial plasma levels of total hemolytic complement, complement factors C3d and C5a, and granulocyte derived elastase were determined immediately before dialysis and sequentially during the entire procedure. Effluent line from the hemodialyzer was similarly sampled. Collected samples were centrifuged immediately at the bedside and instantly frozen in liquid nitrogen in order to preserve labile plasma components of complement. Analysis of the overall results shows that initial arterial leukopenia and generation of C5a in the hemodialyzer, as well as maximal values of hemodialysis-induced free plasma C3d and granulocyte elastase are related. Reflecting differences in biocompatibility, CP membranes were shown to induce significantly more leukopenia, increase in plasma free C3d, generation of C5a, and release of granulocyte-derived elastase. These results indicate that activation of complement, leukopenia, and release of granulocyte derived elastase are interlinked pathophysiological mechanisms of importance for acute deterioration of pulmonary function during hemodialysis, and that this condition is closely related to adult respiratory distress syndrome (ARDS).

Adult↗

The reversibility of cytosolic dehydrogenase reactions in hepatocytes from starved and fed rats. Effect of fructose.

The metabolism of [2-3H]lactate was studied in isolated hepatocytes from fed and starved rats metabolizing ethanol and lactate in the absence and presence of fructose. The yields of 3H in ethanol, water, glucose and glycerol were determined. The rate of ethanol oxidation (3 mumol/min per g wet wt.) was the same for fed and starved rats with and without fructose. From the detritiation of labelled lactate and the labelling pattern of ethanol and glucose, we calculated the rate of reoxidation of NADH catalysed by lactate dehydrogenase, alcohol dehydrogenase and triosephosphate dehydrogenase. The calculated flux of reducing equivalents from NADH to pyruvate was of the same order of magnitude as previously found with [3H]ethanol or [3H]xylitol as the labelled substrate [Vind & Grunnet (1982) Biochim. Biophys. Acta 720, 295-302]. The results suggest that the cytoplasm can be regarded as a single compartment with respect to NAD(H). The rate of reduction of acetaldehyde and pyruvate was correlated with the concentration of these metabolites and NADH, and was highest in fed rats and during fructose metabolism. The rate of reoxidation of NADH catalysed by lactate dehydrogenase was only a few per cent of the maximal activity of the enzymes, but the rate of reoxidation of NADH catalysed by alcohol dehydrogenase was equal to or higher than the maximal activity as measured in vitro, suggesting that the dissociation of enzyme-bound NAD+ as well as NADH may be rate-limiting steps in the alcohol dehydrogenase reaction.

Animals↗

Accumulation of triacylglycerol in cultured rat hepatocytes is increased by ethanol and by insulin and dexamethasone.

Isolated hepatocytes from female rats were cultured in HI-WO/BA medium for 6 days. To the medium was added oleate, ethanol, dexamethasone and insulin. With oleate To alone, triacylglycerol accumulated; ethanol augmented the accumulation by 90%. To the best of our knowledge, this is the first demonstration that ethanol in vitro increases the content of triacylglycerol in liver cells. Further addition of dexamethasone or insulin did not alter the accumulation of triacylglycerol, indicating that these hormones did not play permissive roles for the effect of ethanol in the present system. Dexamethasone and insulin, in the absence of ethanol, increased the accumulation of triacylglycerol by 30% and 50% respectively. The concentration of glycerol 3-phosphate was increased in the presence of ethanol; however, with time the concentration of glycerol 3-phosphate declined almost to control values, while the accumulation of triacylglycerol continued linearly; this suggests that the effect of ethanol was not mediated via fluctuations in the concentration of glycerol 3-phosphate. These results are discussed in relation to earlier investigations in vivo and in vitro.

Animals↗

Interaction of cytoplasmic dehydrogenases: quantitation of pathways of ethanol metabolism.

The interaction between xylitol, alcohol and lactate dehydrogenase has been studied in hepatocytes from rats by applying specifically tritiated substrates. A simple model, describing the metabolic fate of tritium from [2-3H] xylitol and (1R) [1-3H]ethanol is presented. The model allows calculation of the specific radioactivity of free, cytosolic NADH, based on transfer of tritium to lactate, glucose and water. From the initial labelling rate of lactate and the specific radioactivity of cytosolic NADH, we have determined the reversible flow through the lactate dehydrogenase catalyzed reaction to 1-5 mumol/min . g wet wt. The results suggest that xylitol, alcohol and lactate dehydrogenase share the same pool of NAD(H) in the cytoplasma. This finding allows estimation of the ethanol oxidation rate by the non-alcohol dehydrogenase pathways from the relative yield of tritium in water and glucose. The calculations are based on a comparison of the fate of the 1-pro-R hydrogen of ethanol and the hydrogen bound to carbon 2 of xylitol or carbon 2 of lactate under identical conditions.

Alcohol Dehydrogenase↗

Effect of ethanol, noradrenaline and 3',5'-cyclic AMP on oxidation of fatty acids and lipolysis in isolated rat hepatocytes.

Improved methods for the determination of the rate of fatty acid oxidation and lipolysis are presented and evaluated. Hepatocytes from fed rats were incubated with 1.3 mM palmitate. The rate of oxidation of exogenous fatty acids was determined with [1-14C]palmitate. The rate of oxidation of endogenous fatty acids was determined either as the difference between total fatty acid oxidation and oxidation of exogenous fatty acids, or as the oxidation of intracellular lipids, prelabelled with 14C. The two methods agreed completely, indicating that the only endogenous source of acetylCoA was fatty acids. The rate of oxidation of exogenous and endogenous fatty acids was estimated to be 858 and 284 nmol C2-units/min 10(8) cells, respectively, and the rate of lipolysis to be 1640 nmol C2-units/min 10(8) cells. Ethanol caused a 17% and 70% inhibition of the oxidation of exogenous and endogenous fatty acids, respectively. Lipolysis was inhibited approximately 10% by ethanol. Noradrenaline was without effect on the oxidation of exogenous and endogenous fatty acids and on lipolysis. 3',5'-Cyclic AMP enhanced the oxidation of exogenous and endogenous fatty acids by 25% and 31%, respectively, and the rate of lipolysis by 38%, suggesting the presence in hepatocytes of a cAMP sensitive lipase.

Animals↗

The normal occurrence of two molecular forms of the eight complement component (C8) and their concentrations in a family with C8 deficiency.

A haemolytically inactive alpha-mobile complement C8 component was identified by crossed immunoelectrophoresis in a 27-year-old male with recurrent meningococcal infections and absence of complement mediated serum haemolytic activity. The patient's serum/plasma contained no demonstrable normal C8. C8 inhibitor activity was not demonstrable in his serum and the alternative activation pathway appeared to be intact. Serum from the proband's parents and both siblings had normal total haemolytic complement activity and they were without symptoms. However, both the normal and the haemolytically inactive C8 protein were demonstrable in their sera. Their normal C8 concentrations were less than one-half of the normal C8 mean value and distinctly below the lowest value found in ten healthy persons. The concentration of the inactive C8 component in the proband's serum was roughly 1 . 5 times higher than that of the other family members, whereas its concentration in sera of the family members was between 1 . 8 and 2 . 5 times the highest concentration found in ten healthy donors, all of whom also had an alpha-mobile C8 in measurable quantities.

Adult↗

Natural killer cell activity during premedication, anaesthesia and surgery.

Natural killer (NK) cell activity of peripheral blood mononuclear cells was measured against K-562 target cells in a 51Cr release assay in eight patients undergoing total hip replacement surgery. Eight consecutive blood samples were taken from each patient. A significant increase of NK cell activity was observed after premedication with diazepam per os. The activity increased further during a combined anaesthesia (thiopentone + N2O + O2 + buprenorphene + pancuronium) and remained increased during surgery. Postoperatively, NK cell activity fell and remained depressed for a period of at least 5 days. The findings of this study indicate that premedication, anaesthesia and surgery cause a rapid and transient increase in NK cell activity, followed by a decline in activity postoperatively. The transient increase in activity may be explained by mobilization of natural killer cells from extravasal space, spleen or lymph nodes into the circulation. The clinical significance of the alterations in NK cell activity is unknown and needs further investigation.

Aged↗

High-dose intravenous immunoglobulin for post-transfusion purpura.

Successful treatment of a case of post-transfusion purpura with high-dose i.v. human immunoglobulin is reported. A 62-year-old multiparous woman developed severe thrombocytopenia in the wake of transfusions given during and after vascular surgery. A platelet alloantibody with anti-Zwa-specificity was demonstrable by an indirect immunofluorescence technique. A single infusion of Sandoglobulin 1 g/kg body weight caused an immediate platelet response with cessation of haemorrhagic manifestations within 12 h, and the platelet count became normal within 3 d. Thrombocytopenia recurred 8 d after the infusion, but one further dose of Sandoglobulin 0.5 g/kg body weight caused definitive reversal of the thrombocytopenia.

Dose-Response Relationship, Drug↗

Malignant histiocytosis. The diagnosis based on chromosomal, immunologic and histiopathologic analysis.

A 38-year-old female suffered for several months from persistent fever without signs of infectious or immunologic disease. 57Co-bleomycin scintigraphy revealed abnormal concentration in the liver. Following a diagnostic laparotomy, the patient died from abdominal haemorrhage. Malignant cell infiltration was demonstrated in a biopsy from the liver. Histiocytic cells were demonstrated in a bone marrow smear obtained shortly before death. Investigation of cultured lymphocytes obtained from the patient the day before she died showed deficiency of T-lymphocytes. Investigations of chromosomes delineated several clones with polyploidi. The diagnosis of malignant histiocytosis was based on erythrophagocytosis, and immunologic and chromosomal aberrations. If malignant histiocytosis is the primary disease, a terminal stage of different diseases or a sign of complication secondary to immuno incompetence (e.g. virus infection) is an open question.

Adult↗

Acute complement activation during an anaphylactoid reaction to blood transfusion and the disappearance rate of C3c and C3d from the circulation.

A patient experienced an anaphylactoid shock after receiving a transfusion with 5-10 ml of leucocyte-depleted blood. Complement measurements revealed pronounced elevation of split products of the third complement factor (C3c and C3d), normal but fluctuating levels of native C3, significantly decreased levels of C4, normal factor B concentrations and low levels of factor B split products. The results indicate complement activation via the classical pathway as a causative mechanism of the anaphylactoid shock, and suggest an antigen-antibody reaction as the etiological factor. The nature of the antigen-antibody reaction initiating the complement activation could not be established. The disappearance rate (T/2) of C3d from the plasma after the acute C-activation was measured to approximately 4 hr, and the half life of C3c was significantly shorter.

Adult↗

Compartmentation of cytosolic dehydrogenases studied by transfer of tritium from labelled substrates into lactate in rat hepatocytes.

This paper describes the transfer of tritium from [2-(3)H]xylitol or (1R)-[1-(3)H]ethanol into lactate in cells from fed rats either untreated or triiodothyronine-treated. The labelling pattern of lactate during the metabolism of [2-(3)H]xylitol or (1R)-[1-(3)H]ethanol follows the equation L = K(1 - e-t/tau) (mumol tritium/mumol lactate). The yield in lactate together with the minimum value of the total flux of reducing equivalents are used to estimate the specific radioactivity of NADH. We have calculated the lactate dehydrogenase-catalysed oxidation rate of NADH from the experimental values of lactate labelling and the specific radioactivity of NADH. We found the calculated flux of reducing equivalents from NADH to pyruvate to be of the same order of magnitude whether labelled ethanol or labelled xylitol was metabolized. We found the flux to be only a few percent of the maximal activity of lactate dehydrogenase. The results obtained suggest that the cytoplasm can be regarded as one compartment, containing a single pool of NAD(H).

Alcohol Oxidoreductases↗