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Biomedical subjects

M Kruger

Publications and source records attributed to M Kruger.

At least 55 records · Page 3Linked to original sources
PubMed1996

Production of granulocyte-macrophage colony-stimulating factor by T cells is regulated by B7 and IL-1 beta.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has proliferation- and differentiation-inducing effects on immature myeloid cells in the bone marrow, and it can modulate the function of several types of mature myeloid cells. We have stimulated purified human T cells with immobilized anti-CD3 or mitogenic anti-CD2 (a combination of monoclonal antibodies 9-1 and 9.6) which could induce GM-CSF production. The cytokines interleukin-1 beta (IL-1 beta) and IL-2 strongly enhanced GM-CSF production, while IL-4, IL-6, GM-CSF, interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF) had no effect. Activation of protein kinase C by phorbol myristate acetate or triggering of CD28 on T cells by monoclonal antibody 9.3 provided accessory signals for enhanced GM-CSF production in activated T cells. Most important, the addition of mouse cells transfected with human B7-1 (CD80), a natural ligand for CD28, provided a potent accessory signal for GM-CSF production by activated T cells, which could not be blocked by cyclosporin A. The effect of IL-1 beta was in fact indirect, and resulted from enhanced IL-2 production, while the effect of B7 resulted from both IL-2-dependent and IL-2-independent pathways. We conclude that antigen-presenting cells (APC) can up-regulate GM-CSF production through IL-1 beta and through CD28 triggering by B7 molecules. As GM-CSF itself up-regulates B7 expression and IL-1 beta production by APC, a bidirectional regulatory feedback pathway between APC and T cells seems to modulate GM-CSF production.

Adult↗
PubMed1996

Granulocyte-macrophage colony-stimulating factor down-regulates CD14 expression on monocytes.

CD14 is a differentiation-stage-linked glycosyl-phophatidyl-inositol-linked glycoprotein on human peripheral blood monocytes and tissue macrophages, which functions as a receptor for lipopolysaccharide. Here, the effects of granulocyte macrophage colony-stimulating factor (GM-CSF1 a cytokine with proliferation- and differentiation-inducing properties on myeloid lineage cells, were studied on CD14 expression by peripheral blood cells. GM-CSF down-regulated the membrane expression of CD14 on monocytes while it up-regulated expression on neutrophils. GM-CSF also decreased the spontaneous release of CD14 in monocyte culture supernatants. Down-regulation of CD14 expression and release was accompanied by a decrease in the mRNA transcript for CD14, suggesting that it most likely reflects an effect on the transcriptional level. The functional significance of this phenomenon, and its potential relation to the terminal differentiation of monocytes, are discussed.

Adult↗
PubMed1996

Granulocyte-macrophage colony-stimulating factor antagonizes the transforming growth factor-beta-induced expression of Fc gamma RIII (CD16) on human monocytes.

Fc-gamma receptor III (Fc gamma RIII, CD16) type A is expressed on natural killer cells, on a small subset of peripheral blood monocytes and on mature macrophages. Along with differentiation into macrophages, monocytes will express Fc gamma RIII when cultured with transforming growth factor-beta (TGF-beta). In view of the involvement of granulocyte-macrophage colony-stimulating factor (GM-CSF) in myeloid cell differentiation, we investigated the effect of this cytokine on Fc gamma RIII expression in cultures of peripheral blood monocytes. GM-CSF antagonized TGF-beta-induced expression of Fc gamma RIII on monocytes in vitro in a dose-dependent way. The effect of GM-CSF persisted in cultures until at least day 7. The suppression was at the mRNA level, as shown by Northern analyses with a CD16 specific probe, and the signalling pathway involved tyrosine kinase activity. Interferon-gamma and interleukin-2 had no effect on the induced expression of Fc gamma RIII by TGF-beta, while interleukin-4, similar to GM-CSF, antagonized this induction. Our findings suggest that regulatory cytokine networks can drive monocytes into different effector functions and differentiation pathways.

Benzoquinones↗
PubMed1995

The effect of iron fortification on the fatty acid composition of plasma and erythrocyte membranes in primary school children with and without iron deficiency.

An intervention study was designed to evaluate the fatty acid (FA) status of children aged 6-11 years before and after iron fortification. Iron-deficient (ID) and matched controls without ID (n = 30) were selected. All children received soup (160 ml) fortified with 20 mg iron and 100 mg vitamin C for 15 weeks on school days. Measurements before and after intervention included dietary intake, haematological and iron status and FA composition of plasma and erythrocyte membranes (EMBs). The prevalence of low plasma ferritin concentration and transferrin saturation decreased in the ID children by 40% and 56%, respectively, with intervention. Plasma FAs reflected dietary FA intake. In comparison with controls, the ID group presented with increased percentage total saturated FAs (SFAs; p = 0.0002) in their EMB phosphatidylcholine (PC) and reduced percentage total polyunsaturated FAs (PUFAs; p = 0.0037) before intervention. Lower total n-3 FAs (p = 0.0070), including eicosapentenoic acid (EPA; p = 0.0034), docosapentenoic acid (DPA; p = 0.0048) and docosahexenoic acid (DHA; p = 0.0058), were observed in the ID group. The EMB phosphatidylethanol-amine (PEA) of the ID children presented with lower percentages of alpha-linolenic acid (ALA; p = 0.0001), EPA (p = 0.0051) and DHA (p = 0.0084) compared to controls before intervention. Iron intervention was associated with an increase (p < 0.05) in the percentage of n-3 FAs in the EMB-PC and EMB-PEA of the ID group to percentages comparable to that in the control group. It appears that iron status can influence FA metabolism of specific n-3 FAs in the EMBs of young children.

Ascorbic Acid↗
PubMed1995

FcR cross-linking on monocytes results in impaired T cell stimulatory capacity.

Presentation of antigen to T lymphocytes without the appropriate co-stimulatory signals results in a state of antigen-specific unresponsiveness. Despite the presumed importance of the B7-CD28 interaction for the initiation and maintenance of T cell-mediated immune responses, relatively few studies have addressed the regulation of B7 expression. We have studied the expression of the CD80 (B7-1) and B7-2 molecules on peripheral blood monocytes following different activation signals, and it was demonstrated that not only IFN-gamma, but also granulocyte macrophage colony stimulating factor can induce CD80 expression on monocytes. In addition, we found that cross-linking of FcR on monocytes strongly inhibits the up-regulation of CD80 and B7-2, with as a functional consequence that the capacity to function as antigen presenting cells (APC) and to stimulate T cell activation is severely impaired. When cultures were prepared in 96-well plates coated with human IgG, stimulation of T cells with allogeneic monocytes resulted only in modest T cell proliferation and no detectable IL-2 secretion as compared with untreated culture plates or plates coated with Fab fragments of human IgG. Under these conditions cross-linking of CD28 on the T cells with specific mAb completely reverted the inhibitory effect observed after culture on IgG-coated plates. Furthermore, FcR cross-linking on monocytes strongly inhibited the capacity of monocytes to induce a specific memory T cell response to viral, bacterial and fungal antigens, whereas the treatment did not impair the capacity of the T cells to respond to pokeweed mitogen, phytohemagglutinin and concanavalin A. We conclude that after FcR cross-linking, the impaired APC function is most likely due to the inability of monocytes to provide the essential co-stimulatory signals to the T cells via the B7-CD28/CTLA-4 interaction.

Antibodies, Monoclonal↗
PubMed1994

The biophysical profile as a tool for prediction of preterm delivery.

Our objective was to determine if any of the following parameters is a predictor of preterm delivery: gestational age, cervical dilatation, or biophysical profile score.Sixty-two women with certain dates, intact membranes, and preterm contractions more frequent than 300 min underwent a 30-min ultrasonographic assessment of fetal breathing movements, fetal tone, fetal movement and amniotic fluid volume, each of which was scored as 0, 1, or 2 before any tocolytics were given. The total score (0-8) was calculated and cervical dilatation was recorded. All women were subsequently placed on tocolytics. Data were analyzed using survival analysis with stepwise regression of the covariates to determine the predictive values of the total score, its individual parameters, gestational age, and cervical dilatation to the outcome variable of hours to delivery. Gestational age, cervical dilatation and time interval to delivery were categorized and entered into a logistic regression model with the total score and its components to determine predictive odds.Total score (p < 0.0001) and cervical dilatation (p < 0.0001) were the most significant variables associated with time interval to delivery, followed by gestational age (p = 0.035). When the individual biophysical parameters were entered into the model, fetal tone (p < 0.0001), cervical dilatation (p < 0.0001) and gestational age (p < 0.014) were the only variables related to time interval to delivery. Predictive odds of delivery in less than 48 h in relation to fetal tone and cervical dilatation were calculated. Total score, fetal tone, and cervical dilatation were strongly associated with time interval to delivery. Our study did not support fetal breathing movements as a predictor of preterm delivery.

Journal Article↗
PubMed1994

The effect of iron fortification on the fatty acid composition of plasma and erythrocyte membranes in primary school children with and without iron-deficiency.

An intervention study was designed to evaluate the fatty acid (FA) status of children aged 6-11 years before and after iron fortification. Iron deficient (ID) and matched controls without ID (n = 30) were selected. All children received soup (160 mL) fortified with 20 mg iron and 100 mg vitamin C for 15 weeks on school days. Measurements before and after intervention included dietary intake, haematological and iron status and FA composition of plasma and erythrocyte membranes (EMBs). The prevalence of low plasma ferritin concentration and transferrin saturation decreased in the ID children by 40% and 56%, respectively, with intervention. Plasma FAs reflected dietary FA intake. In comparison with controls, the ID group presented with increased percentage total saturated FAs (SFAs; p = 0.0002) in their EMB phosphatidylcholine (PC) and reduced percentage total polyunsaturated FAs (PUFAs; p = 0.0037) before intervention. Lower total n-3 FAs (p = 0.0070) including eicosapentaenoic acid (EPA; p = 0.0034), docosapentaenoic acid (DPA; p = 0.0048) and docosahexaenoic acid (DHA; p = 0.0058) were observed in the ID group. The EMB phosphatidylethanolamine (PEA) of the ID children presented with lower percentages of alpha-linolenic acid (ALA; p = 0.0001), EPA (p = 0.0051) and DHA (p = 0.0084) compared to controls before intervention. Iron intervention was associated with an increase (p < 0,05) in the percentage of n-3 FAs in the EMB-PC and -PEA of the ID group to percentages comparable to that in the control group. It appears that iron status can influence FA metabolism of specific n-3 FAs in the EMBs of young children.

Child↗
PubMed1994

Free cholesterol concentrations in the high-density lipoprotein subfraction-3 as a risk indicator in patients with angiographically documented coronary artery disease.

BACKGROUND: The pathophysiology of plasma lipoprotein metabolism has long been linked to coronary artery disease (CAD). The present study evaluated the association between plasma lipoprotein lipid and apolipoprotein (apo) components and CAD in a group of 80 consecutive Caucasian patients undergoing coronary angiography. METHODS: Coronary cineangiography was carried out using the Judkins technique and the lesions quantified by calculating a coronary artery lesion score (CALS). Very low- and low-density lipoproteins (VLDL and LDL) were separated by ultracentrifugation, and high-density lipoprotein (HDL) and HDL subfraction-3 (HDL3) isolated by a differential precipitation procedure. Apo A-I, A-II, and B were assayed by endpoint laser nephelometry using specific antibodies. Total cholesterol, free cholesterol, and fatty acid concentrations were measured by gas-liquid chromatography, and lecithin: cholesterol acyltransferase (LCAT) activity by the decrease in the concentration of free cholesterol. RESULTS: On the basis of the presence of CAD, the 80 patients were divided into two groups: 52 (65%) with CAD (mean CALS = 7.8) and 28 (35%) without CAD (zero CALS). The lipoprotein fraction that most clearly differentiated the groups was HDL cholesterol concentration, with a mean +/- SEM value of 36.5 +/- 1.5 mg/dl for those with CAD and 45.1 +/- 2.1 mg/dl for those without (P < 0.01). The mean HDL3 cholesterol concentration was 29.9 +/- 1.2 mg/dl for patients with CAD and 37.4 +/- 1.8 mg/dl for those without (P < 0.001). These differences in HDL cholesterol and HDL3 cholesterol were mainly caused by differences in the free cholesterol component, with a mean HDL free cholesterol level of 10.8 +/- 1.1 and 16.1 +/- 1.4 mg/dl (P < 0.01), and a mean HDL3 free cholesterol level of 7.6 +/- 0.6 and 11.9 +/- 0.8 mg/dl (P < 0.001) in patients with and without CAD, respectively. Plasma LCAT activity was decreased in patients with CAD (P < 0.05), as were the apo A-I and A-II concentrations in both the HDL (P < 0.001) and HDL3 (P < 0.001) fractions. No significant association was found between CAD and HDL2 cholesterol or plasma total cholesterol, LDL cholesterol, or VLDL cholesterol concentrations. A stepwise discriminant analysis revealed that HDL3 free cholesterol was the only variable selected. Using HDL3 free cholesterol as a screening variable for CAD (cutoff 10.55 mg/dl), the sensitivity for CAD was 87% and the specificity for non-CAD 67%. The positive and negative predictive values of HDL3 free cholesterol were 82 and 75%, respectively. CONCLUSION: We have shown that the concentrations of HDL cholesterol and HDL3 most clearly differentiated between patients with and without CAD.

Adult↗
PubMed1994

Expression patterns of Fc gamma receptors, HLA-DR and selected adhesion molecules on monocytes from normal and HIV-infected individuals.

The expression and co-expression profiles of functionally important monocyte surface markers were compared between control and HIV+ individuals using combined physical gating and dim CD4 expression to delineate the monocytes. The Fc gamma RII (CD32), the MHC class II antigen HLA-DR and the adhesion molecules CD11a (LFA-1 alpha), CD18 and CD54 (ICAM-1) showed an unimodal distribution. Of these markers, CD11a and HLA-DR were up-regulated in the HIV+ subjects compared with controls. The expression levels of the adhesion molecules correlated with each other in both patients and controls. The CD11b (CR3-alpha), CD14, Fc gamma RI, and Fc gamma RIII markers were bimodally distributed. Compared with controls, monocytes from seropositives contained fewer CD14bright+ cells, an equal proportion of Fc gamma RIbright+ cells, but twice as many Fc gamma RIII+ cells. The expression level of Fc gamma RI and CD11b within their brightly positive subset increased as CD4 T cells decreased. Both in patients and controls, co-expression of bright CD11b, CD14 and Fc gamma RI was shown, whereas the Fc gamma RIII+ cells were negative or dim positive for the former triad. We conclude that the expression of two Fc gamma R (I and III), of the adhesion molecules CD11a and CD11b and of HLA-DR showed particular alterations on monocytes from HIV+ subjects. The relationship of these phenotypic observations with altered cytokine profiles and altered monocyte function is discussed.

Antigens, CD↗
PubMed1993

Ratings of fetal alcohol syndrome facial features by medical providers and biomedical scientists.

Medical providers, (obstetricians, pediatricians) and biomedical research scientists engaged in fetal alcohol research for many years evaluated facial photographs of newborns previously diagnosed clinically as having or not having fetal alcohol syndrome (FAS). Medical providers and biomedical scientists did not differ significantly in their ratings. Children independently diagnosed as having FAS were distinguished from non-FAS children by both groups. Providing raters with additional information about children (e.g., birth weight) did not alter judgements significantly. Raters were highly consistent in the ratings they assigned to children (r = 0.96). Accuracy was assessed using signal detection measures (e.g., likelihood ratio, d'). Based on these measures, the two occupational groups did not differ significantly, and rater accuracy was highly significant. Mean ratings were highly correlated with positive maternal Michigan Alcohol Screening Test scores (r = 0.84). These results suggest that the facial features associated with fetal alcohol exposure are readily identifiable, and this, in turn, implies that recognition problems need not be a major contributor to ascertainment of FAS.

Alcohol Drinking↗
PubMed1993

Parathyroid hormone, ionised calcium, and potentially interacting variables in plasma of an Old World primate.

Bone turnover and calcium homeostasis in man can only be modelled validly in Old World nonhuman primates. In order to interpret the models it is necessary to establish endocrine and biochemical parameters of bone mineral metabolism. This report is probably the first description of acute phase parathyroid responses to manipulations of blood ionised calcium, and of reference values for potentially interacting variables, in vervet monkeys. Plasma parathyroid hormone concentrations were measured in vervets under defined conditions, and ranges reported as normal for other nonhuman primates and man are summarised.

Animals↗
PubMed1992

Fat, protein and carbohydrate content of diets of white insulin-dependent diabetic adolescents and young adults.

Dietary habits and serum cholesterol levels were surveyed in 39 young insulin-dependent diabetic subjects (mean age (+/- SD) 17.7 +/- 4.0 years, 21 females, 18 males). All had received the routine dietary advice that total carbohydrate, fat and protein consumption should constitute more than 45-50%, less than 30-35% and less than 20% respectively of total energy intake. Of the subjects 27 (69%) consumed more fat and 21 (54%) less carbohydrate than recommended. Fat consumption correlated positively with total energy (r = 0.747; P less than 0.00001) and negatively with carbohydrate intake (r = -0.757; P less than 0.00001), suggesting that restrictions placed on carbohydrate energy sources were offset by greater fat ingestion. Serum cholesterol exceeded the recommended ideal of 5.2 mmol/l in over half the subjects, and correlated positively with body mass index. Dietary advice to insulin-dependent diabetic patients must emphasise the freer consumption of unrefined carbohydrates, so as to reduce fat intake.

Adolescent↗
PubMed1992

Reversible hypophosphatemic rickets following ifosfamide treatment.

A 7-year-old boy developed renal tubular dysfunction and hypophosphatemic rickets following treatment for relapsed embryonal rhabdomyosarcoma. Multi-agent chemotherapy included ifosfamide; the child received a total of 108 g/m2. The complete Fanconi syndrome which ensued, including excessive loss of calcium, resolved spontaneously and progressively 18 months after the last dose of ifosfamide. The patient had no further symptoms of rickets and radiological signs had almost completely normalized. Further follow-up was not possible as, despite further treatment, the child died of progressive disease.

Abdominal Neoplasms↗
PubMed1992

Comparison of the effect of the amount and degree of unsaturation of dietary fat on plasma low density lipoproteins in vervet monkeys.

The effects of the degree of unsaturation and of the amount of dietary fat on low density lipoprotein (LDL) concentration and composition were determined in vervet monkeys. Diets with fat contents of 41, 31 and 18% energy, each with a low and a high polyunsaturated to saturated fatty acid ratio (P/S; 0.27-0.38 and 1.13-1.47) were fed to six female vervet monkeys for two months. Another six females were given a low fat, high P/S diet for the same period of time, to serve as a reference. The cholesterol contents of the diets were low (21-33 mg per day) and relatively constant. LDL cholesterol concentrations decreased significantly (P < or = 0.01) when the dietary fat content decreased from 31 to 18% of energy. The dietary P/S ratio only affected LDL cholesterol concentrations during moderate (31% of energy) fat intake, where LDL cholesterol increased (P < or = 0.01) with a decrease in dietary P/S. Substantial individual variations were observed in LDL cholesterol concentration responses to dietary fat changes. The changes in LDL cholesterol concentrations were the result of changes in the concentration of LDL particles, as the molecular composition did not differ significantly between dietary periods. The high density lipoprotein cholesterol and the plasma triacylglycerol concentrations were not influenced by the dietary fat changes. During the high P/S diets, the percentage of 18:2 (linoleic acid) increased (P < or = 0.01) and that of 18:1 (oleic acid) decreased (P < or = 0.01) in LDL esterified cholesterol, as compared to the low P/S diets. In adipose tissue triacylglycerol the percentage of 18:2 was three times higher (P < or = 0.01) during the high P/S diets than during the low P/S diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1992

The influence of fish oil supplementation on plasma lipoproteins and arterial lipids in vervet monkeys with established atherosclerosis.

There is controversy about whether supplementing diets with marine fish oil can regress, promote or prevent atherosclerosis. Therefore the effects of an Atlantic pilchard oil (FO) supplement and dietary change were measured in a proven atherosclerosis model. Vervet or African Green monkeys were fed an atherogenic diet (AD) for long enough to ensure progression before treatments started. Matched groups were then treated for 20 months, either by adding FO to the AD (AD/FO), or by changing to a therapeutic diet with FO (TD/FO). Control treatments consisted of supplementing with sunflower oil (SO) instead of FO, so that treatments were AD/SO and TD/SO. The same total polyunsaturates were supplied by the FO and SO and the dose of FO was realistic (2.5% of total energy). A reference group (R) received the TD with no oil supplements. Supplementing with FO did not change the concentrations of total, low or high density lipoprotein cholesterol in plasma. After The AD/FO the intimas of aortas contained more total (p < or = 0.001), free (p < or = 0.05) and esterified (p < or = 0.05) cholesterol, total phospholipid (p < or = 0.01) and sphingomyelin (p < or = 0.05) than after the AD/SO. After FO supplementation eicosapentaenoic acid was significantly higher and arachidonic acid significantly lower in the plasma and aorta intima phosphatidylcholine. None of these changes was anti-atherogenic in terms of atherosclerosis measured in the same individuals (1). Nor did FO increase the efficacy of the TD.

Animals↗
PubMed1992

Influence of dietary protein on glomerular filtration and urinary albumin excretion in insulin-dependent diabetes.

We investigated the effects of dietary constituents on glomerular filtration (GFR) and albumin excretion rates (AERs) in a cross-sectional study in 39 young subjects with insulin-dependent diabetes. Dietary protein intake correlated significantly in patients with GFRs less than 150 mL/min per 1.73 m2 (r = 0.53, n = 23, P = 0.009), but not with AER. GFR also correlated with mean blood glucose at a concentration less than 12.0 mmol/L (r = 0.61, P = 0.0035). Protein and fat intakes were similar in patients with and without microalbuminuria (AER greater than 20 mg/L) but long-term glycemic control was worse in the former [HbA1 12.4 +/- 2.9% (mean +/- SD) and 10.6 +/- 2.1%, respectively, P = 0.043]. In seven patients, short-term reduction of dietary protein from 2.0 to 1.0 to 0.5 g.kg-1.d-1 produced a progressive fall in GFR by 11.6 +/- 6.0 and 9.6 +/- 5.9 mL/min, respectively (P less than 0.05), but did not consistently affect AER. We conclude that both dietary protein and glycemic control influence GFR but neither alone appears to explain glomerular hyperfiltration. Microalbuminuria was associated with poor glycemic control but not with dietary fat or protein consumption.

Adolescent↗