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F Hugo

Publications and source records attributed to F Hugo.

At least 19 recordsLinked to original sources
PubMed2006

A simple and practical agglutination assay for human leucocyte antigen-B27 typing.

BACKGROUND AND OBJECTIVES: The human leucocyte antigen (HLA) B27 is the most frequently typed single antigen that is associated with diseases. Here, we describe a simple and rapid particle agglutination assay (PaGIA) for HLA-B27 typing. MATERIALS AND METHODS: Superparamagnetic particles were coated with a monoclonal antibody to HLA-B27 and subsequently used for testing. Anticoagulated whole-blood samples were obtained from healthy blood donors (n = 194) with known HLA patterns and from patients (n = 51) who had been typed positive for HLA-B27 by flow cytometry. RESULTS: The particles agglutinated only after incubation with HLA-27-positive blood samples, using the ID-microtyping system. Positive reactions were clearly distinguishable from negative reactions in all samples tested. Flow cytometric HLA-B27 typing revealed an indeterminate result in one patient. CONCLUSIONS: The new HLA-B27 PaGIA is suitable for rapid typing of HLA-B27. The assay is simple and easy to perform, and can be implemented in any routine laboratory.

Agglutination Tests↗
PubMed2004

Headaches in patients with systemic lupus erythematosus: a comparative study.

The incidence and nature of headaches in 85 systemic lupus erythematosus (SLE) patients attending an outpatient clinic were studied and compared to those experienced by 61 nurses. The two groups were similar in age, sex and ethnicity. Test-retest assessment of reliability gave both groups 95% confidence limits of 0.09-0.21. Thirty-two (38%) patients developed migrainous headaches and nine (10%) stress headaches with the onset of lupus. In the control group, four (6%) developed migraine and 40 (66%) developed stress headaches on commencing work. We could not document any association of headaches with flares of systemic disease, the ACA syndrome, Raynaud's phenomenon or increased SLEDAI score. We conclude that migrainous headaches are more common in lupus patients than healthy controls, but in an outpatient setting are not statistically associated with flares of systemic disease.

Adolescent↗
PubMed2001

Serum concentrations of some metals and steroids in patients with chronic fatigue syndrome with reference to neurological and cognitive abnormalities.

Chronic fatigue syndrome is defined by the Atlanta Centers for Disease Control (Atlanta, GA, USA) as debilitating fatigue lasting for longer than 6 months. Symptoms include disturbances of cognition. Certain factors have in the past been shown to influence cognition, including metals such as aluminum, iron, and zinc; and steroids such as dehydroepiandrosterone. In the present study, concentrations of these factors were determined in the serum and plasma of patients and their age- and gender-matched healthy controls (10 women and 5 men in each group). In addition, copper, dehydroepiandrosterone sulphate, cortisol, cholesterol, hemoglobin, ferritin and transferrin concentrations, as well as transferrin genetic subtypes were determined in both groups. The results indicate that patients had significantly increased serum aluminum and decreased iron compared to controls. In the females, serum iron and dehydroepiandrosterone sulphate were significantly decreased and correlated. Total cholesterol was significantly increased, and significantly negatively correlated with dehydroepiandrosterone sulphate. There were no differences in zinc, copper, cortisol, hemoglobin, transferrin and ferritin concentrations, or in transferrin genetic subtypes.

Adult↗
PubMed1999

Are musical obsessions a temporal lobe phenomenon?

Obsessive musical tunes have been described in some cases of obsessive-compulsive disorder (OCD). The authors present 2 cases of patients with musical obsessions, including findings from functional brain imaging. Both patients, 1 with idiopathic OCD and 1 with symptoms secondary to head trauma, demonstrated decreased blood flow in temporal lobes. This finding is consistent with previous literature on musical and auditory hallucinations.

Adult↗
PubMed1999

Functional brain imaging in obsessive-compulsive disorder secondary to neurological lesions.

UNLABELLED: Obsessive-compulsive disorder (OCD) may result from a range of neurological lesions in frontal and basal ganglia areas. However, relatively few studies have explored functional brain imaging in acquired OCD. METHODS: Charts of patients presenting to our Neuropsychiatry Unit where obsessive-compulsive symptoms appeared secondary to neurological lesions were reviewed. Demographic information and clinical diagnoses were collated, and brain SPECT scans reviewed. Six patients with various neurological conditions presented with OCD. All demonstrated decreased blood flow in the temporal lobes as well as cortical perfusion abnormalities in the frontal lobes (focal areas of decreased perfusion in one patient, focal areas of increased perfusion in two, and a combination of focal increased and decreased frontal perfusion in three cases). Abnormal blood flow may be seen in a number of different brain regions in acquired OCD. It is unclear whether these changes reflect primary neurological lesions or secondary changes to compensate for such damage. However, increased frontal blood flow in OCD may be hypothesized to reflect a compensatory mechanism.

Adult↗
PubMed1997

Teratomas in infancy and childhood at Tygerberg Hospital, South Africa, 1973 to 1992.

OBJECTIVES: To document the childhood teratomas at Tygerberg Hospital and compare the profile with other African series. DESIGN: Retrospective review of the clinicopathologic features of 43 cases of childhood teratomas. Tumors were classified according to the World Health Organization criteria for germ cell tumors. SETTING: Tygerberg Hospital, University of Stellenbosch, Cape Town, South Africa. RESULTS: There were 26 mature, 15 immature, and 2 malignant teratomas. The most common sites were the ovaries and the sacrococcygeal region. Testicular teratomas were absent. The female-to-male ratio for black patients was 5.5:1. There was a peak age incidence in the first 4 years of life, with sacrococcygeal teratomas predominating. A second, smaller peak between 12 and 15 years was seen owing to ovarian teratomas. Immature teratomas presented at an earlier age than mature teratomas. The majority of ovarian teratomas occurred in patients of mixed race, whereas the extragonadal teratomas were distributed more evenly among the race groups. In black patients and patients of mixed race mature teratomas predominated, whereas in white patients immature teratomas were most common. CONCLUSIONS: The increased occurrence of teratomas among female patients, the large number of ovarian teratomas, the absence of testicular teratomas, and the low incidence of malignant teratomas correspond to the observations of other African series. Certain differences are apparent among the three race groups, namely, a high ratio of female-to-male patients in the black group, a predominance of ovarian teratomas in the mixed-race and black groups, and a predominance of extragonadal and immature teratomas in the white group.

Adolescent↗
PubMed1996

Studies on associations of glycolytic and glutaminolytic enzymes in MCF-7 cells: role of P36.

Isoelectric focusing of MCF-7 cell extracts revealed an association of the glycolytic enzymes glyceraldehyde 3-phosphate-dehydrogenase, phosphoglycerate kinase, enolase, and pyruvate kinase. This complex between the glycolytic enzymes is sensitive to RNase. p36 could not be detected within this association of glycolytic enzymes; however an association of p36 with a specific form of malate dehydrogenase was found. In MCF-7 cells three forms of malate dehydrogenase can be detected by isoelectric focusing: the mitochondrial form with an isoelectric point between 8.9 and 9.5, the cytosolic form with pl 5.0, and a p36-associated form with pl 7.8. The mitochondrial form comprises the mature mitochondrial isoenzyme (pl 9.5) and its precursor form (pl 8.9). Refocusing of the pl 7.8 form of malate dehydrogenase also gave rise to the mitochondrial isoenzyme. Thus, the pl 7.8 form of malate dehydrogenase is actually the mitochondrial isoenzyme retained in the cytosol by the association with p36. Addition of fructose 1,6-bisphosphate to the initial focusing column induced a quantitative shift of the pl 7.8 form of malate dehydrogenase to the mitochondrial forms (pl 8.9 and 9.5). In MCF-7 cells p36 is not phosphorylated in tyrosine. Kinetic measurements revealed that the pl 7.8 form of malate dehydrogenase has the lowest affinity for NADH. Compared to both mitochondrial forms the cytosolic isoenzyme has a high capacity when measured in the NAD --> NADH direction (malate --> oxaloacetate direction). The association of p36 with the mitochondrial isoenzyme may favor the flow of hydrogen from the cytosol into the mitochondria. Inhibition of cell proliferation by AMP which leads to an inhibition of glycolysis has no effect on complex formation by glycolytic and glutaminolytic enzymes in MCF-7 cells. AMP treatment leads to an activation of malate dehydrogenase, which correlates with the increase of pyruvate and the decrease of lactate levels, but has no effect on the distribution of the various malate dehydrogenase forms.

Adenosine Monophosphate↗
PubMed1996

Influence of the terminal complement-complex on reperfusion injury, no-reflow and arrhythmias: a comparison between C6-competent and C6-deficient rabbits.

OBJECTIVE: The complement system has been suggested to play a role in reperfusion injury which may result from an enhanced destruction of myocardial tissue or from an impairment of reflow. We investigated the influence of the C5b-9 complement complex on infarct size, reflow and arrhythmogenesis. METHODS: Twenty-eight C6-competent rabbits and 18 rabbits with congenital C6 deficiency were subjected to either 30 min or 2 h of coronary artery occlusion followed by reperfusion. C6 deficiency was confirmed by the complement titration test and immunohistology. The triphenyl tetrazolium chloride method was used to delineate infarct size. Reflow into infarcted areas was evaluated histologically after an in vivo injection of propidium iodide which served as an early fluorescence microscopic marker of damaged myocardium subjected to reflow. Continuous ECG monitoring allowed the recording of arrhythmias. RESULTS: After 30 min of coronary artery occlusion infarct size was significantly smaller in C6-deficient rabbits (5.0 +/- 2% of the risk region) as compared to C6-competent rabbits (28.4 +/- 8.5%, P = 0.0371). The extent of reflow into damaged myocardium was nearly the same in both animal groups at this time (38 +/- 9 vs. 39 +/- 7% of the risk region). After 2 h of coronary artery occlusion, infarct size was not different between both animal groups, but the extent of reflow into damaged myocardium was significantly smaller in C6-competent rabbits than in C6-deficient rabbits (25 +/- 4 vs. 40 +/- 4%; P = 0.0185). Two of the 18 C6-deficient rabbits had ventricular arrhythmias (Lown II-IV), none of which was fatal. Eleven of the 28 C6-competent animals had major ventricular arrhythmias which were fatal in 6 rabbits. CONCLUSIONS: These results suggest that the lytic C5b-9 complement complex leads to reperfusion injury in the early phase (30 min) of ischaemia, resulting in a larger infarct. After 2 h of ischaemia, complement activation enhances the no-reflow phenomenon but does not affect infarct size. Finally, the C6 status seems to influence the susceptibility to ventricular arrhythmias after coronary artery occlusion, independent of reperfusion.

Animals↗
PubMed1996

MRI in children given gadodiamide injection: safety and efficacy in CNS and body indications.

The safety and efficacy of the MRI contrast medium gadodiamide injection (OMNISCAN) in children is summarised. Four open and three double-blind, multinational, multicentre comparative trials have been undertaken. Overall, 353 patients (15 days to 18 years, plus one 21 years) received gadodiamide injection, and 128 (2-18 years) received gadopentetate dimeglumine (Magnevist), intravenously at 0.1 mmol/kg body weight, to aid the identification of CNS and body lesions. Adverse events were reported in 13 (4%) patients given gadodiamide injection and 8 (6%) given gadopentetate dimeglumine; few patients reported injection-associated discomfort. The post-contrast scan gave more diagnostic information in 223 (63%) patients given gadodiamide injection (CNS and body indications). In the comparative trials, the post-contrast scan gave more diagnostic information for 91 (65%) and 82 (64%) patients given gadodiamide injection and gadopentetate dimeglumine, respectively (CNS indications only). Gadodiamide injection (0.1 mmol/kg body weight) was safe and effective in infants, children and adolescents.

Adolescent↗
PubMed1995

Binding of antibodies to functional epitopes on the pore formed by Escherichia coli hemolysin in cells and model membranes.

Escherichia coli hemolysin (HlyA) inserts into target membranes producing a cation-selective pore. We approached the problem of determining which portions of this protein remain exposed on the side of attack by applying specific antibodies. Results obtained with resealed erythrocyte ghosts and planar phospholipid membranes were compared. The effects of one polyclonal and four monoclonal anti-hemolysin antibodies (mAbs) were studied. Using ghosts we found one mAb which strongly reduced the ion-permeability through the preinserted HlyA channels and one which clearly increased it. Experiments with planar bilayers corroborated these results by showing that the former mAb effectively promoted the closed state of the channel whereas the latter forced the HlyA channel into an open configuration. Anti-hemolysin polyclonal antibodies initially stimulated but then prevented channel opening, indicating they contained clones able to act on both these channel determinants. They were effective only when applied on the same side as the hemolysin indicating that the epitopes were exposed to that side. Finally, the antigenic epitopes of three of the mAbs were localised on the HlyA molecule by using different mutants (amber and frame shift mutants and hemolysin gene hybrids).

Animals↗
PubMed1994

Early accumulation of the terminal complement-complex in the ischaemic myocardium after reperfusion.

The terminal, membrane-damaging complement complex C5b-9 accumulates in the infarcted myocardium. In experimental myocardial infarction, we investigated the time course of C5b-9 deposition and the influence of reperfusion. In a group of 17 rabbits (group 1), the circumflex coronary artery was occluded for different time periods ranging from 0.5 to 29 h without subsequent reperfusion. A second group of 23 rabbits (group 2) underwent coronary artery occlusion for periods ranging from 0.5 to 6 h followed by reperfusion. C5b-9 was determined in transmural myocardial biopsies by immunohistochemistry and by ELISA. In group 1, C5b-9 accumulation in the ischaemic myocardium was found only after 5 to 6 h of coronary artery occlusion. In group 2 (ischaemia and reperfusion), significant C5b-9 deposition was already observed after 30 min of myocardial ischaemia. We conclude that in the absence of reperfusion C5b-9 accumulation occurs as a late event when most of the jeopardized myocardium has probably already become necrotic. In the presence of reperfusion, however, the complement system is activated rapidly and this could play a role in the pathogenesis of reperfusion injury.

Animals↗
PubMed1992

In vitro effect of extracellular AMP on MCF-7 breast cancer cells: inhibition of glycolysis and cell proliferation.

MCF-7 human breast cancer cells propagated in vitro were treated with adenosine derivatives added to the culture medium. The effects on cell proliferation, glycolysis, and glutaminolysis were investigated. Of all adenosine derivatives tested, AMP was the most efficient inhibitor of cell proliferation. In AMP-treated cells, DNA synthesis decreased, whereas RNA and protein syntheses rose normally with time. In terms of carbohydrate metabolism, lactate production from glucose was drastically reduced; therefore, most of lactate produced must have been derived from glutamine. Increases in the enzyme activities involved in glutamate degradation and in the malate-aspartate shuttle were observed. In contrast, actual glycolytic flux rates declined, whereas key glycolytic enzyme activities increased. Metabolites such as fructose 1,6-bisphosphate and pyruvate accumulated in AMP-arrested cells. Based on the lowered NAD level in the AMP-treated cells, lactate dehydrogenase, but not malate dehydrogenase, was impaired; thereby the whole of glycolysis was inhibited. In compensation, glutamine catabolism was increased. NAD concentrations fell drastically because of the known inhibition of P-ribose-PP synthesis through heightened intracellular AMP levels. A hypothetical metabolic scheme to explain these results and to show how extracellular AMP may influence carbohydrate metabolism and cell proliferation is presented.

Adenosine Monophosphate↗
PubMed1991

Lung vascular injury after administration of viable hemolysin-forming Escherichia coli in isolated rabbit lungs.

Escherichia coli hemolysin, a transmembrane pore-forming exotoxin, is considered an important virulence factor. In the present study, the possible significance of hemolysin production was investigated in a model of septic lung failure through infusion of viable bacteria in isolated rabbit lungs; 10(4) to 10(7) E. coli/ml perfusate caused a dose- and time-dependent appearance of hemolysin, accompanied by release of potassium, thromboxane A2, and PGI2 into the perfusate. Concomitantly, marked pulmonary hypertension developed. Inhibitor studies suggested that the pressor response was predominantly mediated by pulmonary thromboxane generation. Administration of hemolysin-forming E. coli additionally caused a protracted, dose-dependent increase in the lung capillary filtration coefficient, followed by severe edema formation. The permeability increase was independent of lung prostanoid generation. An E. coli strain that releases an inactive form of hemolysin completely failed to provoke the described biophysical and biochemical responses. Preapplication of 2 x 10(8) human granulocytes was without effect in the present experimental model. We conclude that the hemolysin produced by low numbers of E. coli organisms can provoke thromboxane-mediated pulmonary hypertension and severe vascular leakage. E. coli hemolysin and, possibly, other related cytolysins may thus contribute directly to the pathogenesis of acute respiratory failure under conditions of sepsis or pneumonia.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Isolation and characterization of a complement-activating lipid extracted from human atherosclerotic lesions.

The major characteristics of human atherosclerotic lesions are similar to those of a chronic inflammatory reaction, namely fibrosis, mesenchymal cell proliferation, the presence of resident macrophages, and cell necrosis. Atherosclerosis exhibits in addition the feature of lipid (mainly cholesterol) accumulation. The results of the present report demonstrate that a specific cholesterol-containing lipid particle present in human atherosclerotic lesions activates the complement system to completion. Thus, lipid could represent a stimulatory factor for the inflammatory reaction, whose underlying mechanistic basis may be, at least in part, complement activation. The complement-activating lipid was purified from saline extracts of aortic atherosclerotic lesions by sucrose density gradient centrifugation followed by molecular sieve chromatography on Sepharose 2B. It contained little protein other than albumin, was 100-500 nm in size, exhibited an unesterified to total cholesterol ratio of 0.58 and an unesterified cholesterol to phospholipid ratio of 1.2. The lipid, termed lesion lipid complement (LCA), activated the alternative pathway of complement in a dose-dependent manner. Lesion-extracted low density lipoprotein (LDL) obtained during the purification procedure failed to activate complement. Specific generation of C3a desArg and C5b-9 by LCA indicated C3/C5 convertase formation with activation proceeding to completion. Biochemical and electron microscopic evaluations revealed that much of the C5b-9 present in atherosclerotic lesions is membraneous, rather than fluid phase SC5b-9. The observations reported herein establish a link between lipid insudation and inflammation in atherosclerotic lesions via the mechanism of complement activation.

Aorta↗
PubMed1990

Functions and relevance of the terminal complement sequence.

The terminal complement sequence is initiated upon cleavage of C5 with liberation of C5a anaphylatoxin, and involves the assembly of macromolecular C5b-9 complexes either on cell surfaces or in plasma. Cell-bound C5b-9 complexes generate transmembrane pores that can cause cell death, or they can elicit secondary cellular reactions triggered, for example, by passive flux of calcium ions into the cells. In vivo functions of the fluid-phase SC5b-9 complex have not yet been defined, but the identity of S-protein with vitronectin (serum spreading factor) provokes the anticipation that significant biological functions of this complex do exist. The terminal complement sequence may fulfil protective functions when it is triggered on alien cells that are marked for destruction. Dysregulation in the complement sequence may, however, result in detrimental attack by C5b-9 on autologous cells. Examples include not only autoimmune disease states, but also the activation of complement on dead or dying cells, and bystander attack on blood cells during cardiopulmonary bypass. Methods for detecting and quantifying C5b-9 are outlined, and the potential usefulness of such assays in clinical research is discussed.

Complement C3-C5 Convertases↗
PubMed1990

Functional similarity between the haemolysins of Escherichia coli and Morganella morganii.

Haemolysin produced by a clinical isolate of Morganella morganii was examined for antigenic relatedness to the haemolysin of Escherichia coli and for similarities in mode of action. The M. morganii haemolysin migrated in SDS-PAGE as a single protein band with a slightly higher molecular weight than that of E. coli haemolysin. Several murine monoclonal antibodies against E. coli haemolysin cross-reacted with the M. morganii haemolysin in Western blots. Diminished haemolysis in the presence of osmotically-stabilising solutes indicated the formation of a pore by M. morganii haemolysin with an effective diameter of 1.5-3 nm. Results from dose-response experiments indicated that a single "hit" was sufficient for lysis of an erythrocyte. Detergent solubilisation of toxin-treated membranes led to recovery of bound toxin exclusively in monomeric form. M. morganii haemolysin was a potent leucocidin, that caused rapid leakage of ATP and death of human polymorphonuclear leucocytes. Under in-vitro conditions M. morganii haemolysin displayed similar leucocidal and haemolytic efficiency. The data demonstrate that M. morganii haemolysin shows functional properties virtually identical with those of E. coli haemolysin.

Adenosine Triphosphate↗
PubMed1990

Quantitative measurement of SC5b-9 and C5b-9(m) in infarcted areas of human myocardium.

Previous immunohistochemical work has indicated that terminal C5b-9 complement complexes are selectively deposited in infarcted areas of human myocardium. In the present study, we sought to quantify C5b-9 levels in myocardial tissue, and to differentiate between the membrane-bound C5b-9 (m) and the cytolytically inactive SC5b-9 complex. Paired tissue specimens from infarcted and non-infarcted myocardium were obtained from 36 autopsies. The homogenized and washed tissues were extracted with n-octyl-beta-D-glucopyranoside (octylglucoside) detergent, and the concentrations of C5b-9 in the extracts were determined by ELISA. Membrane-derived C5b-9 (m) and SC5b-9 were differentiated from each other on the basis of their characteristic sedimentation behaviour in sucrose density gradients. It was found that infarcted myocardial tissue contained on average an approximately three-fold higher concentration of C5b-9, compared with non-infarcted tissue. This increase was due in part to an increase in levels of C5b-9 (m). The results corroborate previous immunohistochemical data and show that complement activation occurs to completion with the generation of potentially cytotoxic C5b-9 complexes in infarcted myocardial tissues.

Adult↗